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Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals 1
2
Davide F. Robbiani1*,#, Christian Gaebler1*, Frauke Muecksch2*, Julio C. C. Lorenzi1*, Zijun 3
Wang1*, Alice Cho1*, Marianna Agudelo1*, Christopher O. Barnes6*, Anna Gazumyan1*, Shlomo 4
Finkin1*, Thomas Hagglof1*, Thiago Y. Oliveira1*, Charlotte Viant1*, Arlene Hurley4, Hans-5
Heinrich Hoffmann3, Katrina G. Millard1, Rhonda G. Kost5, Melissa Cipolla1, Kristie Gordon1, 6
Filippo Bianchini1, Spencer T. Chen1, Victor Ramos1, Roshni Patel1, Juan Dizon1, Irina 7
Shimeliovich1, Pilar Mendoza1, Harald Hartweger1, Lilian Nogueira1, Maggi Pack1, Jill Horowitz1, 8
Fabian Schmidt2, Yiska Weisblum2, Eleftherios Michailidis3, Alison W. Ashbrook3, Eric Waltari7, 9
John E. Pak7, Kathryn E. Huey-Tubman6, Nicholas Koranda6, Pauline R. Hoffman6, Anthony P. 10
West, Jr.6, Charles M. Rice3, Theodora Hatziioannou2, Pamela J. Bjorkman6, Paul D. Bieniasz2,8,#, 11
Marina Caskey1,#, Michel C. Nussenzweig1,8,# 12
13
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA 14 2Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA 15 3Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 16 10065, USA 17 4Hospital Program Direction, The Rockefeller University, New York, NY 10065, USA 18 5Hospital Clinical Research Office, The Rockefeller University, New York, NY 10065, USA 19 6Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, 20 CA 91125, USA 21 7Chan Zuckerberg Biohub, 499 Illinois Street, San Francisco, CA 94158, USA 22 8Howard Hughes Medical Institute 23 *Equal contribution 24 #Send correspondence to Paul D. Bieniasz: [email protected], Marina Caskey: 25 [email protected], Michel C. Nussenzweig: [email protected], or Davide F. 26 Robbiani: [email protected] 27
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Abstract 28
During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed 29
hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain 30
(RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that 31
antibodies will be essential for protection. However, little is known about the human 32
antibody response to SARS-CoV-21-5. Here we report on 149 COVID-19 convalescent 33
individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable 34
half-maximal neutralizing titers ranging from undetectable in 33% to below 1:1000 in 79%, 35
while only 1% showed titers >1:5000. Antibody cloning revealed expanded clones of RBD-36
specific memory B cells expressing closely related antibodies in different individuals. Despite 37
low plasma titers, antibodies to three distinct epitopes on RBD neutralized at half-maximal 38
inhibitory concentrations (IC50s) as low as single digit ng/mL. Thus, most convalescent 39
plasmas obtained from individuals who recover from COVID-19 do not contain high levels 40
of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent 41
antiviral activity were found in all individuals tested, suggesting that a vaccine designed to 42
elicit such antibodies could be broadly effective. 43
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Between April 1 and May 8, 2020, 157 eligible participants enrolled in the study. Of these, 111 44
(70.7%) were individuals diagnosed with SARS-CoV-2 infection by RT-PCR (cases), and 46 45
(29.3%) were close contacts of individuals diagnosed with SARS-CoV-2 infection (contacts). 46
While inclusion criteria allowed for enrollment of asymptomatic participants, 8 contacts that did 47
not develop symptoms were excluded from further analyses. The 149 cases and contacts were free 48
of symptoms suggestive of COVID-19 for at least 14 days at the time of sample collection. 49
Participant demographics and clinical characteristics are shown in Table 1 and Extended Data 50
Tables 1 and 2. Only one individual who tested positive for SARS-CoV-2 infection by RT-PCR 51
remained asymptomatic. The other 148 participants reported symptoms suggestive of COVID-19 52
with an average onset of approximately 39 days (range 17 to 67 days) before sample collection. In 53
this cohort, symptoms lasted for an average of 12 days (0-35 days), and 11 (7%) of the participants 54
were hospitalized. The most common symptoms were fever (83.9%), fatigue (71.1%), cough 55
(62.4%) and myalgia (61.7%) while baseline comorbidities were infrequent (10.7%) (Table 1 and 56
Extended Data Tables 1 and 2). There were no significant differences in duration or severity (see 57
Methods) of symptoms, or in time from onset of symptoms to sample collection between genders 58
or between cases and contacts. There was no age difference between females and males in our 59
cohort (Extended Data Fig. 1). 60
61
Plasma samples were tested for binding to the SARS-CoV-2 RBD and trimeric spike (S) proteins 62
by ELISA using anti-IgG or -IgM secondary antibodies for detection (Fig. 1, Extended Data Table 63
1 and Extended Data Figs. 2 and 3). Eight independent negative controls and the plasma sample 64
from participant 21 (COV21) were included for normalization of the area under the curve (AUC). 65
Overall, 78% and 70% of the plasma samples tested showed anti-RBD and anti-S IgG AUCs that 66
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were at least 2 standard deviations above the control (Fig. 1 a, b). In contrast, only 15% and 34% 67
of the plasma samples showed IgM responses to anti-RBD and anti-S that were at least 2 standard 68
deviations above control, respectively (Fig. 1 c, d). There was no positive correlation between anti-69
RBD or -S IgG or IgM levels and duration of symptoms or the timing of sample collection relative 70
to onset of symptoms (Fig. 1e, and Extended Data Figs. 3 a-c and 3 g-j). On the contrary, as might 71
be expected, anti-RBD IgM titers were negatively correlated with duration of symptoms and the 72
timing of sample collection (Fig. 1e and Extended Data Fig. 3h). Anti-RBD IgG levels were 73
modestly correlated to age, and the severity of symptoms including hospitalization (Fig. 1 f, g and 74
Extended Data Fig. 3k). Interestingly, females had lower anti-RBD and -S IgG titers than males 75
(Fig. 1h, Extended Data Fig. 2f). 76
77
To measure the neutralizing activity in convalescent plasmas we used HIV-1-based virions 78
carrying a nanoluc luciferase reporter that were pseudotyped with the SARS-CoV-2 spike (SARS-79
CoV-2 pseudovirus, see Methods, Fig. 2 and Extended Data Fig. 4). The overall level of 80
neutralizing activity in the cohort, as measured by the half-maximal neutralizing titer (NT50) was 81
generally low, with 33% undetectable and 79% below 1,000 (Fig. 2 a, b). The geometric mean 82
NT50 was 121 (arithmetic mean = 714), and only 2 individuals reached NT50s above 5,000 (Fig. 2 83
a, b and Extended Data Table 1). 84
85
Notably, levels of anti-RBD- and -S IgG antibodies correlated strongly with NT50 (Fig. 2 c, d). 86
Neutralizing activity also correlated with age, duration of symptoms and symptom severity 87
(Extended Data Fig. 5). Consistent with this observation, hospitalized individuals with longer 88
symptom duration showed slightly higher average levels of neutralizing activity than non-89
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hospitalized individuals (p=0.0495, Fig. 2e). Finally, we observed a significant difference in 90
neutralizing activity between males and females (p=0.0031, Fig. 2f). The difference between males 91
and females was consistent with higher anti-RBD and -S IgG titers in males, and could not be 92
attributed to age, severity, timing of sample collection relative to onset of symptoms or duration 93
of symptoms (Fig. 1h, Extended Data Fig. 1 a-d and 2f). 94
95
To determine the nature of the antibodies elicited by SARS-CoV-2 infection we used flow 96
cytometry to isolate individual B lymphocytes with receptors that bound to RBD from the blood 97
of 6 selected individuals including the 2 top and 4 high to intermediate neutralizers (Fig. 3). The 98
frequency of antigen-specific B cells, identified by their ability to bind to both Phycoerythrin (PE)- 99
and AF647-labeled RBD, ranged from 0.07 to 0.005% of all circulating B cells in COVID-19 100
convalescents but they were undetectable in pre-COVID-19 controls (Fig. 3a and Extended Data 101
Fig. 6). We obtained 534 paired IgG heavy and light chain (IGH and IGL) sequences by reverse 102
transcription and subsequent PCR from individual RBD-binding B cells from the 6 convalescent 103
individuals (see Methods and Extended Data Table 3). When compared to the human antibody 104
repertoire, several IGHV and IGLV genes were significantly over-represented (Extended Data Fig. 105
7). The average number of V genes nucleotide mutations for IGH and IGL was 4.2 and 2.8, 106
respectively (Extended Data Fig. 8), which is lower than in antibodies cloned from individuals 107
suffering from chronic infections such as Hepatitis B or HIV-1, and similar to antibodies derived 108
from primary malaria infection or non-antigen-enriched circulating IgG memory cells6-8 (Wang et 109
al, in press, https://www.biorxiv.org/content/10.1101/2020.03.04.976159v1.full). Among other 110
antibody features, IGH CDR3 length was indistinguishable from the reported norm and 111
hydrophobicity was below average (Extended Data Fig. 8)9. 112
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113
As is the case with other human pathogens, there were expanded clones of viral antigen binding B 114
cells in all COVID-19 individuals tested (see Methods and Fig. 3 b,c). Overall, 32.2% of the 115
recovered IGH and IGL sequences were from clonally expanded B cells (range 21.8-57.4% across 116
individuals, Fig. 3b). Antibodies that shared specific combinations of IGHV and IGLV genes in 117
different individuals comprised 14% of all the clonal sequences (colored pie slices in Fig. 3 b,c). 118
Remarkably, the amino acid sequences of some antibodies found in different individuals were 119
nearly identical (Fig. 3 e,d). For example, antibodies expressed by clonally expanded B cells with 120
IGHV1-58/IGKV3-20 and IGHV3-30-3/IGKV1-39 found repeatedly in different individuals had 121
amino acid sequence identities of up to 99% and 92%, respectively (Fig. 3d and Extended Data 122
Table 4). We conclude that the IgG memory response to the SARS-CoV-2 RBD is rich in recurrent 123
and clonally expanded antibody sequences. 124
125
To examine the binding properties of anti-SARS-CoV-2 antibodies, we expressed 84 126
representative antibodies, 56 from clones and 28 from singlets (Extended Data Table 5). ELISA 127
assays showed that 94% (79 out of 84) of the antibodies tested including clonal and unique 128
sequences bound to the SARS-CoV-2 RBD with an average half-maximal effective concentration 129
(EC50) of 6.1 ng/mL (Fig. 4a and Extended Data Fig. 9a). A fraction of those (7 out of 79, or 9%) 130
cross-reacted with the RBD of SARS-CoV with a mean EC50 of 120.1 ng/mL (Extended Data Fig. 131
9b and c). No significant cross-reactivity was noted to the RBDs of MERS, HCoV-OC43, HCoV-132
229E or HCoV-NL63. 133
134
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To determine whether the monoclonal antibodies have neutralizing activity, we tested them against 135
the SARS-CoV-2 pseudovirus (Fig. 4 and Extended Data Table 6). Among 79 RBD binding 136
antibodies tested, we found 40 that neutralized SARS-CoV-2 pseudovirus with nanogram per 137
milliliter half-maximal inhibitory concentrations (IC50s) ranging from 3 to 709 (Fig. 4 b,c and e, 138
Extended Data Table 6). A subset of the most potent of these antibodies were also tested against 139
authentic SARS-CoV-2 and neutralized with IC50s of less than 5 ng/ml (Fig. 4 d,e). 140
141
Potent neutralizing antibodies were found in individuals irrespective of their plasma NT50s. For 142
example, C121, C144, and C135 with IC50s of 1.64, 2.55 and 2.98 ng/mL against authentic SARS-143
CoV-2, respectively, were obtained from individuals COV107, COV47, and COV72 whose 144
plasma NT50 values were of 297, 10,433 and 3,138, respectively (Figs. 2b and 4). Finally, clones 145
of antibodies with shared IGHV and IGLV genes were among the best neutralizers, e.g., antibody 146
C002 composed of IGHV3-30/IGKV1-39 is shared by the 2 donors with the best plasma 147
neutralizing activity (red pie slice in Fig. 3b and Fig. 4). We conclude that even individuals with 148
modest plasma neutralizing activity harbor rare IgG memory B cells that produce potent SARS-149
CoV-2 neutralizing antibodies. 150
151
To determine whether human anti-SARS-CoV-2 monoclonal antibodies with neutralizing activity 152
can bind to distinct domains on the RBD, we performed bilayer interferometry experiments in 153
which a preformed antibody-RBD immune complex was exposed to a second monoclonal. The 154
antibodies tested comprised 3 groups, all of which differ in their binding properties from CR3022, 155
an antibody that neutralizes SARS-CoV and binds to, but does not neutralize SARS-CoV-210,11. 156
Representatives of each of the 3 groups include: C144 and C101 in Group 1; C121 and C009 in 157
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Group 2; C135 in Group 3. All of these antibodies can bind after CR3022. Groups 1 and 2 also 158
bind after Group 3, and Groups 1 and 2 differ in that Group 1 can bind after Group 2 but not vice 159
versa (Fig. 4 f-n). We conclude that similar to SARS-CoV, there are multiple distinct neutralizing 160
epitopes on the RBD of SARS-CoV-2. 161
162
To further define the binding characteristics of Groups 1 and 2 antibodies, we imaged SARS-CoV-163
2 S–Fab complexes by negative stain electron microscopy (nsEM) using C002 (Group 1, an 164
IGHV3-30/IGKV1-39 antibody, which is clonally expanded in 2 donors), C119 and C121 (both in 165
Group 2) Fabs (Fig. 4 f-r and Extended Data Fig. 10). Consistent with the conformational 166
flexibility of the RBD, 2D class averages showed heterogeneity in both occupancy and 167
conformation of bound Fabs for both groups (Fig. 4o-q). The 3D reconstructions of S-Fab 168
complexes revealed both a fully-occupied RBD and partial density for a second bound Fab, 169
suggesting that Fabs from both groups are able to recognize “up” and “down” states of the RBD 170
as previously described for some of the antibodies targeting this epitope12,13. The 3D 171
reconstructions are also consistent with BLI measurements indicating that Groups 1 and 2 172
antibodies bind a RBD epitope distinct from antibody CR3022, which is only accessible on the 173
RBD “up” conformational state11, and bind the RBD with different angles of approach, with Group 174
1 antibodies most similar to the approach angle of the SARS-CoV antibody S230 (Fig. 4r)14. 175
176
Human monoclonal antibodies with neutralizing activity against pathogens ranging from viruses 177
to parasites have been obtained from naturally infected individuals by single cell antibody cloning. 178
Several have been shown to be effective in protection and therapy in model organisms and in early 179
phase clinical studies, but only one antiviral monoclonal is currently in clinical use15. Antibodies 180
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are relatively expensive and more difficult to produce than small molecule drugs. However, they 181
differ from drugs in that they can engage the host immune system through their constant domains 182
that bind to Fc gamma receptors on host immune cells16. These interactions can enhance immunity 183
and help clear the pathogen or infected cells, but they can also lead to disease enhancement during 184
Dengue17 and possibly coronavirus infections18. This problem has impeded Dengue vaccine 185
development but would not interfere with the clinical use of potent neutralizing antibodies that can 186
be modified to prevent Fc gamma receptor interactions and remain protective against viral 187
pathogens19. 188
189
Antibodies are essential elements of most vaccines and will likely be crucial component of an 190
effective vaccine against SARS-CoV-220(PMID:32434945; PMID:32434946). Recurrent 191
antibodies have been observed in other infectious diseases and vaccinal responses 21-24(Wang et 192
al, in press, https://www.biorxiv.org/content/10.1101/2020.03.04.976159v1.full). The observation 193
that plasma neutralizing activity is low in most convalescent individuals, but that recurrent anti-194
SARS-CoV-2 RBD antibodies with potent neutralizing activity can be found in individuals with 195
unexceptional plasma neutralizing activity suggests that humans are intrinsically capable of 196
generating anti-RBD antibodies that potently neutralize SARS-CoV-2. Thus, vaccines that 197
selectively and efficiently induce antibodies targeting the SARS-CoV-2 RBD may be especially 198
effective. 199
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Table 200
201
Table 1. Cohort characteristics
Gender n IgG IgM IgG IgM45 12 39 5.8
(19-76) (0-31) (21-63) (0-10)42 12 38 5.4
(19-75) (1-35) (17-67) (1-9)Sx=symptoms
867
Female 66 46/20 1.99 1.58 4.36 1.86 522
2.44 1.61
Averageage
83Male 65/18
ELISA binding (AUC)RBD S
4.65 1.62
Case/Contact
Average duration Average Sx Severity
(0-10)Neutralization
(NT50)Sx
totalSx onset to visit
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Figures 202
203
Figure 1. Plasma antibodies against SARS-CoV-2. a-d, Graphs show results of ELISAs 204
measuring plasma reactivity to RBD (a, b) and S protein (c, d). Left shows optical density units at 205
450 nm (OD, Y axis) and reciprocal plasma dilutions (X axis). Negative controls in black; 206
individuals 21, and 47 in blue and red lines and arrowheads, respectively. Right shows normalized 207
area under the curve (AUC) for controls and each of 149 individuals in the cohort. e, Symptom 208
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(Sx) onset to time of sample collection in days (X axis) plotted against normalized AUC for IgM 209
binding to RBD (Y axis) r=0.5517 and p=<0.0001. f, Participant age in years (X axis) plotted 210
against normalized AUC for IgG binding to RBD (Y axis) r=0.1827 and p=0.0258. The r and p 211
values for the correlations in e and f were determined by two-tailed Spearman’s. g, IgG anti-RBD 212
normalized AUC for outpatients and hospitalized individuals p=0.0178. h, IgG anti-RBD 213
normalized AUC for males and females p=0.0063. For g and h horizontal bars indicate median 214
values. Statistical significance was determined using two-tailed Mann-Whitney U test. 215
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216
Figure 2. Neutralization of SARS-CoV-2 pseudovirus by plasma. a, Graph shows normalized 217
relative luminescence values (RLU, Y axis) in cell lysates of 293TACE2 cells 48 hours after 218
infection with nanoluc-expressing SARS-CoV-2 pseudovirus in the presence of increasing 219
concentrations of plasma (X axis) derived from 149 participants (grey, except individuals 47 and 220
21 in red, and blue lines, bars and arrowheads, respectively) and 3 negative controls (black lines). 221
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Standard deviations of duplicates of one representative experiment are shown. b, Ranked average 222
half-maximal inhibitory plasma neutralizing titer (NT50) for the 59 of 149 individuals with NT50s 223
>500 and individual 107. See also Extended Data Table 1. Asterisks indicate donors from which 224
antibody sequences were derived. c, AUC for anti-RBD IgG ELISA (X axis) plotted against NT50 225
(Y axis) r=0.6432, p=<0.0001. d, AUC for anti-S IgG ELISA (X axis) plotted against NT50 (Y 226
axis) r=0.6721, p=<0.0001. e, NT50 for outpatients and hospitalized individuals p=0.0495. f, NT50 227
for all males and females in the cohort p=0.0031. Dotted line in c to f (NT50=5) represents lower 228
limit of detection (LLOD). Samples with undetectable neutralizing titers were plotted at LLOD. 229
Correlations in c and d were determined by two-tailed Spearman’s. Statistical significance in e and 230
f was determined using two-tailed Mann-Whitney U test. Horizontal bars indicate median values. 231
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232
Figure 3. Anti-SARS-CoV-2 RBD antibodies. a. Representative flow cytometry plots showing 233
dual AF647- and PE-RBD binding B cells in control and 6 study individuals (for gating strategy 234
see Extended Data Fig. 6). Percentages of antigen specific B cells are indicated. Control is a 235
healthy control sample obtained pre-COVID-19. b, Pie charts depicting the distribution of 236
antibody sequences from 6 individuals. The number in the inner circle indicates the number of 237
sequences analyzed for the individual denoted above the circle. White indicates sequences isolated 238
only once, and grey or colored pie slices are proportional to the number of clonally related 239
sequences. Red, blue, orange and yellow pie slices indicate clones that share the same IGHV and 240
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IGLV genes. c, Circos plot shows sequences from all 6 individuals with clonal relationships 241
depicted as in b. Interconnecting lines indicate the relationship between antibodies that share V 242
and J gene segment sequences at both IGH and IGL. Purple, green and gray lines connect related 243
clones, clones and singles, and singles to each other, respectively. d, Sample sequence alignment 244
for antibodies originating from different individuals that display highly similar IGH V(D)J and 245
IGL VJ sequences including CDR3s. Amino acid differences in CDR3s to the bolded reference 246
sequence above are indicated in red and dots represent identities. 247
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248
Figure 4. Anti-SARS-CoV-2 RBD antibody reactivity. a, Graph show results of ELISA assays 249
measuring monoclonal antibody reactivity to RBD. Optical density units at 450 nm (OD, Y axis) 250
vs. antibody concentrations (X axis). C121, C135 C144 and isotype control in red, green, purple, 251
and black respectively, in all panels. b, Graph shows normalized relative luminescence values 252
(RLU, Y axis) in cell lysates of 293TACE2 cells 48 hours after infection with SARS-CoV-2 253
pseudovirus in the presence of increasing concentrations of monoclonal antibodies (X axis). c, 254
RLU for SARS-CoV-2 pseudovirus assay (Y axis) vs. titration of monoclonal antibodies C121, 255
C135 and C144 in one of two independent experiments (see Extended Data Table 6). d, SARS-256
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CoV-2 real virus neutralization assay. Infected cells (Y axis) vs. titration of monoclonal antibodies 257
C121, C135 and C144 in two independent experiments. For a and b panels, isotype control 258
antibody in black. e, IC50s for antibodies assayed in b and d. f, Diagrammatic representation of 259
biolayer interferometry experiment. g, Graph shows binding of C144, C101, C121, C009, C135, 260
and CR302210,11 to RBD. h-m, Secondary antibody binding to preformed IgG-RBD complexes 261
(Ab1). The table displays the shift in nanometers after second antibody (Ab2) binding to the 262
antigen in the presence of the first antibody (Ab1). Values are normalized by the subtraction of the 263
autologous antibody control. o-q, Representative 2D-class averages and 3D reconstructed 264
volumes for SARS-CoV-S 2P trimers complexed with C002, C119, and C121 Fabs. 2D-class 265
averages with observable Fab density are boxed. r, Overlay of S-Fab complexes with fully-266
occupied C002 (blue), C121 (magenta) and C119 (orange) Fabs aligned on the RBD “up” 267
conformational state. The SARS-CoV-2 S model with 1 “up” RBD state (PDB 6VYB) was fit into 268
the density and the SARS-CoV antibody S230 (PDB 6NB6) shown as reference (green ribbon). 269
270
271
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Methods 272
Study participants. Study participants were recruited at the Rockefeller University Hospital in 273
New York from April 1 through May 8, 2020. Eligible participants were adults aged 18-76 years 274
who were either diagnosed with SARS-CoV-2 infection by RT-PCR and were free of symptoms 275
of COVID-19 for at least 14 days (cases), or who were close contacts (e.g., household, co-workers, 276
members of same religious community) with someone who had been diagnosed with SARS-CoV-277
2 infection by RT-PCR and were free of symptoms suggestive of COVID-19 for at least 14 days 278
(contacts). Exclusion criteria included presence of symptoms suggestive of active SARS-CoV-2 279
infection, or hemoglobin < 12 g/dL for males and < 11 g/dL for females. 280
Most study participants were residents of the Greater New York City tri-state region and were 281
enrolled sequentially according to eligibility criteria. Participants were first interviewed by phone 282
to collect information on their clinical presentation, and subsequently presented to the Rockefeller 283
University Hospital for a single blood sample collection. Participants were asked to rate the 284
highest severity of their symptoms on a numeric rating scale ranging from 0 to 10. The score was 285
adapted from the pain scale chart, where 0 was the lack of symptoms, 4 were distressing symptoms 286
(e.g. fatigue, myalgia, fever, cough, shortness of breath) that interfered with daily living activities, 287
7 were disabling symptoms that prevented the performance of daily living activities, and 10 was 288
unimaginable/unspeakable discomfort (in this case, distress due to shortness of breath). All 289
participants provided written informed consent before participation in the study and the study was 290
conducted in accordance with Good Clinical Practice. 291
292
Blood samples processing and storage. Peripheral Blood Mononuclear Cells (PBMCs) were 293
obtained by gradient centrifugation and stored in liquid nitrogen in the presence of FCS and 294
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DMSO. Heparinized plasma and serum samples were aliquoted and stored at -20°C or less. Prior 295
to experiments, aliquots of plasma samples were heat-inactivated (56C for 1 hour) and then stored 296
at 4C. 297
298
Cloning, expression and purification of recombinant coronavirus proteins. Codon-optimized 299
nucleotide sequences encoding the SARS-CoV-2 S ectodomain (residues 16-1206) and receptor 300
binding domain (RBD; residues 331-524) were synthesized and subcloned into the mammalian 301
expression pTwist-CMV BetaGlobin vector by Twist Bioscience Technologies based on an early 302
SARS-CoV-2 sequence isolate (GenBank MN985325.1). The SARS-CoV-2 RBD construct 303
included an N-terminal human IL-2 signal peptide and dual C-terminal tags ((GGGGS)2-304
HHHHHHHH (octa-histidine), and GLNDIFEAQKIEWHE (AviTag)). In addition, the 305
corresponding S1B or receptor binding domains for SARS-CoV S (residues 318-510; GenBank 306
AAP13441.1), MERS-CoV S (residues 367-588; GenBank JX869059.2), HCoV-NL63 (residues 307
481-614; GenBank AAS58177.1), HCoV-OC43 (residues 324-632; GenBank AAT84362.1), and 308
HCoV-229E (residues 286-434; GenBank AAK32191.1) were synthesized with the same N- and 309
C-terminal extensions as the SARS-CoV-2 RBD construct and subcloned into the mammalian 310
expression pTwist-CMV BetaGlobin vector (Twist Bioscience Technologies). The SARS-CoV-2 311
S ectodomain was modified as previously described 4. Briefly, the S ectodomain construct included 312
an N-terminal mu-phosphatase signal peptide, 2P stabilizing mutations (K986P and V987P), 313
mutations to remove the S1/S2 furin cleavage site (682RRAR685 to GSAS), a C-terminal extension 314
(IKGSG-RENLYFQG (TEV protease site), GGGSG-YIPEAPRDGQAYVRKDGEWVLLSTFL 315
(foldon trimerization motif), G-HHHHHHHH (octa-histidine tag), and GLNDIFEAQKIEWHE 316
(AviTag)). The SARS-CoV-2 S 2P ectodomain and RBD constructs were produced by transient 317
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transfection of 500 mL of Expi293 cells (Thermo Fisher) and purified from clarified transfected 318
cell supernatants four days post-transfection using Ni2+-NTA affinity chromatography (GE Life 319
Sciences). Affinity-purified proteins were concentrated and further purified by size-exclusion 320
chromatography (SEC) using a Superdex200 16/60 column (GE Life Sciences) running in 1x TBS 321
(20 mM Tris-HCl pH 8.0, 150 mM NaCl, and 0.02% NaN3). Peak fractions were analyzed by SDS- 322
PAGE, and fractions corresponding to soluble S 2P trimers or monomeric RBD proteins were 323
pooled and stored at 4˚C. 324
325
ELISAs. ELISAs to evaluate antibodies binding to SARS-CoV-2 RBD and trimeric spike proteins 326
were performed by coating of high binding 96 half well plates (Corning #3690) with 50 µL per 327
well of a 1µg/mL protein solution in PBS overnight at 4°C. Plates were washed 6 times with 328
washing buffer (1xPBS with 0.05% Tween 20 (Sigma-Aldrich)) and incubated with 170 µL per 329
well blocking buffer (1xPBS with 2% BSA and 0.05% Tween20 (Sigma)) for 1 hour at room 330
temperature (RT). Immediately after blocking, monoclonal antibodies or plasma samples were 331
added in PBS and incubated for 1 hr at RT. Plasma samples were assayed at a 1:200 starting 332
dilution and seven additional 3-fold serial dilutions. Monoclonal antibodies were tested at 10µg/ml 333
starting concentration and 10 additional 4-fold serial dilutions. Plates were washed 6 times with 334
washing buffer and then incubated with anti-human IgG or IgM secondary antibody conjugated to 335
horseradish peroxidase (HRP) (Jackson Immuno Research 109-036-088 and 109-035-129) in 336
blocking buffer at a 1:5000 dilution. Plates were developed by addition of the HRP substrate, TMB 337
(ThermoFisher) for 10 minutes, then the developing reaction was stopped by adding 50µl 1M 338
H2SO4 and absorbance was measured at 450nm with an ELISA microplate reader (FluoStar 339
Omega, BMG Labtech). For plasma samples, a positive control (plasma from patient COV21, 340
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diluted 200-fold in PBS) was added in duplicate to every assay plate. The average of its signal was 341
used for normalization of all the other values on the same plate with Excel software prior to 342
calculating the area under the curve using Prism 8 (GraphPad). For monoclonal antibodies, the 343
half-maximal effective concentration (EC50) was determined using 4-parameter nonlinear 344
regression (GraphPad Prism). 345
346
293TACE2 cells. For constitutive expression of ACE2 in 293T cells, a cDNA encoding ACE2, 347
carrying two inactivating mutations in the catalytic site (H374N & H378N), was inserted into CSIB 348
3’ to the SFFV promoter25. 293TACE2 cells were generated by transduction with CSIB based virus 349
followed by selection with 5 µg/ml Blasticidin. 350
351
SARS-CoV-2 and SARS-CoV pseudotyped reporter viruses. A plasmid expressing a C-352
terminally truncated SARS-CoV-2 S protein (pSARS-CoV2-Strunc) was generated by insertion of 353
a human-codon optimized cDNA encoding SARS-CoV-2 S lacking the C-terminal 19 codons 354
(Geneart) into pCR3.1. The S ORF was taken from “Wuhan seafood market pneumonia virus 355
isolate Wuhan-Hu-1” (NC_045512). For expression of full-length SARS-CoV S protein, “Human 356
SARS coronavirus Spike glycoprotein Gene ORF cDNA clone expression plasmid (Codon 357
Optimized)” (here referred to as pSARS-CoV-S) was obtained from SinoBiological (Cat: 358
VG40150-G-N). An env-inactivated HIV-1 reporter construct (pNL4-3DEnv-nanoluc) was 359
generated from pNL4-326 by introducing a 940 bp deletion 3’ to the vpu stop-codon, resulting in a 360
frameshift in env. The human codon-optimized nanoluc Luciferase reporter gene (Nluc, Promega) 361
was inserted in place of nucleotides 1-100 of the nef-gene. To generate pseudotyped viral stocks, 362
293T cells were transfected with pNL4-3DEnv-nanoluc and pSARS-CoV2-Strunc or pSARS-CoV-363
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S using polyethyleneimine. Co-transfection of pNL4-3DEnv-nanoluc and S-expression plasmids 364
leads to production of HIV-1-based virions carrying either the SARS-CoV-2 or SARS-CoV spike 365
protein on the surface. Eight hours after transfection, cells were washed twice with PBS and fresh 366
media was added. Supernatants containing virions were harvested 48 hours post transfection, 367
filtered and stored at -80°C. Infectivity of virions was determined by titration on 293TACE2 cells. 368
369
Pseudotyped virus neutralization assay. Five-fold serially diluted plasma from COVID-19 370
convalescent individuals and healthy donors or four-fold serially diluted monoclonal antibodies 371
were incubated with the SARS-CoV-2 or SARS-CoV pseudotyped virus for 1 hour at 37°C 372
degrees. The mixture was subsequently incubated with 293TACE2 cells for 48 hours after which 373
cells were washed twice with PBS and lysed with Luciferase Cell Culture Lysis 5x reagent 374
(Promega). Nanoluc Luciferase activity in lysates was measured using the Nano-Glo Luciferase 375
Assay System (Promega). Relative luminescence units obtained were normalized to those derived 376
from cells infected with SARS-CoV-2 or SARS-CoV pseudotyped virus in the absence of plasma 377
or monoclonal antibodies. The half-maximal inhibitory concentration for plasma (NT50) or 378
monoclonal antibodies (IC50) was determined using 4-parameter nonlinear regression (GraphPad 379
Prism). 380
Cell lines, virus and virus titration. VeroE6 kidney epithelial cells (Chlorocebus sabaeus) and 381
Huh-7.5 hepatoma cells (H. sapiens) were cultured in Dulbecco’s Modified Eagle Medium 382
(DMEM) supplemented with 1% nonessential amino acids (NEAA) and 10% fetal bovine serum 383
(FBS) at 37oC and 5% CO2. All cell lines have been tested negative for contamination with 384
mycoplasma and were obtained from the ATCC (with the exception for Huh-7.5). 385
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SARS-CoV-2, strain USA-WA1/2020, was obtained from BEI Resources and amplified in VeroE6 386
cells at 33°C. Viral titers were measured on Huh-7.5 cells by standard plaque assay (PA). Briefly, 387
500 µL of serial 10-fold virus dilutions in Opti-MEM were used to infect 400,000 cells seeded the 388
day prior in a 6-well plate format. After 90 min adsorption, the virus inoculum was removed, and 389
cells were overlayed with DMEM containing 10% FBS with 1.2% microcrystalline cellulose 390
(Avicel). Cells were incubated for five days at 33°C, followed by fixation with 3.5% formaldehyde 391
and crystal violet staining for plaque enumeration. All experiments were performed in a biosafety 392
level 3 laboratory. 393
Microscopy-based neutralization assay of authentic SARS-CoV-2. The day prior to infection 394
VeroE6 cells were seeded at 12,500 cells/well into 96-well plates. Antibodies were serially diluted 395
in BA-1, mixed with a constant amount of SARS-CoV-2 (grown in VeroE6) and incubated for 60 396
min at 37°C. The antibody-virus-mix was then directly applied to VeroE6 cells (MOI of ~0.1 397
PFU/cell). Cells were fixed 18 hours post infection by adding an equal volume of 7% formaldehyde 398
to the wells, followed by permeabilization with 0.1% Triton X-100 for 10 min. After extensive 399
washing, cells were incubated for 1 hour at room temperature with blocking solution of 5% goat 400
serum in PBS (catalog no. 005–000-121; Jackson ImmunoResearch). A rabbit polyclonal anti-401
SARS-CoV-2 nucleocapsid antibody (catalog no. GTX135357; GeneTex) was added to the cells 402
at 1:500 dilution in blocking solution and incubated at 4°C overnight. A goat anti-rabbit 403
AlexaFluor 594 (catalog no. A-11012; Life Technologies) at a dilution of 1:2,000 was used as a 404
secondary antibody. Nuclei were stained with Hoechst 33342 (catalog no. 62249; Thermo 405
Scientific) at a 1:1,000 dilution. Images were acquired with a fluorescence microscope and 406
analyzed using ImageXpress Micro XLS (Molecular Devices, Sunnyvale, CA). All statistical 407
analyses were done using Prism 8 software (GraphPad). 408
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Biotinylation of viral protein for use in flow cytometry. Purified and Avi-tagged SARS-CoV-2 409
RBD was biotinylated using the Biotin-Protein Ligase-BIRA kit according to manufacturer’s 410
instructions (Avidity). Ovalbumin (Sigma, A5503-1G) was biotinylated using the EZ-Link Sulfo-411
NHS-LC-Biotinylation kit according to the manufacturer’s instructions (Thermo Scientific). 412
Biotinylated Ovalbumin was conjugated to streptavidin-BV711 (BD biosciences, 563262) and 413
RBD to streptavidin-PE (BD biosciences, 554061) and streptavidin-Alexa Fluor 647 (AF647, 414
Biolegend, 405237) respectively27. 415
416
Single cell sorting by flow cytometry. PBMCs were enriched for B cells by negative selection 417
using a pan B cell isolation kit according to the manufacturer’s instructions (Miltenyi Biotec, 130-418
101-638). The enriched B cells were incubated in FACS buffer (1 X Phosphate-buffered Saline 419
(PBS), 2% calf serum, 1 mM EDTA) with the following anti-human antibodies: anti-CD20-PECy7 420
(BD Biosciences, 335793), anti-CD3-APC-eFluro 780 (Invitrogen, 47-0037-41), anti-CD8-APC-421
eFluro 780 (Invitrogen, 47-0086-42), anti-CD16-APC-eFluro 780 (Invitrogen, 47-0168-41), anti-422
CD14-APC-eFluro 780 (Invitrogen, 47-0149-42), as well as Zombie NIR (BioLegend, 423105), 423
and fluorophore-labeled RBD and Ovalbumin for 30 minutes on ice27. Single CD3-CD8-CD16-424
CD20+Ova-RBD-PE+RBD-AF647+ B cells were sorted into individual wells of a 96-well plates 425
containing 4 μl of lysis buffer (0.5 X PBS, 10mM DTT, 3000 units/mL RNasin Ribonuclease 426
Inhibitors (Promega, N2615) per well using a FACS Aria III (Becton Dickinson). The sorted cells 427
were frozen on dry ice, and then stored at −80°C or immediately used for subsequent RNA reverse 428
transcription. Although cells were not stained for IgG expression, they are memory B cells based 429
on the fact that they are CD20+ (a marker absent in plasmablasts) and they express IgG (since 430
antibodies were amplified from these cells using IgG-specific primers). 431
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432
Antibody sequencing, cloning and expression. Antibodies were identified and sequenced as 433
described previously22,28,29. Briefly, RNA from single cells was reverse-transcribed (SuperScript 434
III Reverse Transcriptase, Invitrogen, 18080-044) and the cDNA stored at -20°C or used for 435
subsequent amplification of the variable IGH, IGL and IGK genes by nested PCR and Sanger 436
sequencing28. Amplicons from the first PCR reaction were used as templates for Sequence- and 437
Ligation-Independent Cloning (SLIC) into antibody expression vectors. Recombinant monoclonal 438
antibodies and Fabs were produced and purified as previously described30,31. 439
440
Biolayer interferometry. 441
BLI assays were performed on the Octet Red instrument (ForteBio) at 30°C with shaking at 1,000 442
r.p.m. Epitope binding assays were performed with protein A biosensor (ForteBio 18-5010), 443
following the manufacture protocol “classical sandwich assay”. (1) Sensor check: sensors 444
immersed 30 sec in buffer alone (buffer ForteBio 18-1105). (2) Capture 1st Ab: sensors immersed 445
10min with Ab1 at 40 µg/mL. (3) Baseline: sensors immersed 30sec in buffer alone. (4) Blocking: 446
sensors immersed 5 min with IgG isotype control at 50 µg/mL. (6) Antigen association: sensors 447
immersed 5 min with RBD at 100 µg/mL. (7) Baseline: sensors immersed 30 sec in buffer alone. 448
(8) Association Ab2: sensors immersed 5min with Ab2 at 40 µg/mL. Curve fitting was performed 449
using the Data analysis software (ForteBio). 450
451
Computational analyses of antibody sequences. Antibody sequences were trimmed based on 452
quality and annotated using Igblastn v1.14.032 with IMGT domain delineation system. Annotation 453
was performed systematically using Change-O toolkit v.0.4.533. Heavy and light chains derived 454
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from the same cell were paired, and clonotypes were assigned based on their V and J genes using 455
in-house R and Perl scripts (Fig. 3 b,c). All scripts and the data used to process antibody sequences 456
are publicly available on GitHub (https://github.com/stratust/igpipeline). 457
The frequency distributions of human V genes in anti-SARS-CoV-2 antibodies from this study 458
was compared to Sequence Read Archive SRP01097034. The V(D)J assignments were done using 459
IMGT/High V-Quest and the frequencies of heavy and light chain V genes were calculated for 14 460
and 13 individuals, respectively, using sequences with unique CDR3s. The two-tailed t test with 461
unequal variances was used to determine statistical significance (Extended Data Fig. 7). 462
Nucleotide somatic hypermutation and CDR3 length were determined using in-house R and Perl 463
scripts. For somatic hypermutations, IGHV and IGLV nucleotide sequences were aligned against 464
their closest germlines using IgBlast and the number of differences were considered nucleotide 465
mutations. The average mutations for V genes was calculated by dividing the sum of all nucleotide 466
mutations across all patients by the number of sequences used for the analysis. To calculate the 467
GRAVY scores of hydrophobicity35 we used Guy H.R. Hydrophobicity scale based on free energy 468
of transfer (kcal/mole)36 implemented by the R package Peptides available in the Comprehensive 469
R Archive Network repository (https://journal.r-project.org/archive/2015/RJ-2015-001/RJ-2015-470
001.pdf). We used 534 heavy chain CDR3 amino acid sequences from this study and 22,654,256 471
IGH CDR3 sequences from the public database of memory B-cell receptor sequences37. The 472
Shapiro-Wilk test was used to determine whether the GRAVY scores are normally distributed. 473
The GRAVY scores from all 533 IGH CDR3 amino acid sequences from this study 474
(sequence COV047_P4_IgG_51-P1369 lacks CDR3 amino acid sequence) were used to perform 475
the test and 5000 GRAVY scores of the sequences from the public database were randomly 476
selected. The Shapiro-Wilk p-values were 6.896 x 10-3 and 2.217 x 10-6 for sequences from this 477
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study and the public database, respectively, indicating the data are not normally distributed. 478
Therefore, we used the Wilcoxon non-parametric test to compare the samples, which indicated a 479
difference in hydrophobicity distribution (p = 5 x 10-6; Extended Data Fig. 8). 480
481
Negative-stain EM Data Collection and Processing 482
Purified Fabs (C002, C119, and C121) were complexed with SARS-CoV-2 S trimer at a 2-fold 483
molar excess for 1 min and diluted to 40 µg/mL in TBS immediately before adding 3 µL to a 484
freshly-glow discharged ultrathin, 400 mesh carbon-coated copper grid (Ted Pella, Inc.). Samples 485
were blotted after a 1 min incubation period and stained with 1% uranyl formate for an additional 486
minute before imaging. Micrographs were recorded on a Thermo Fisher Talos Arctica transmission 487
electron microscope operating at 200 keV using a K3 direct electron detector (Gatan, Inc) and 488
SerialEM automated image acquisition software38. Images were acquired at a nominal 489
magnification of 28,000x (1.44 Å/pixel size) and a -1.5 to -2.0 µm defocus range. Images were 490
processed in cryoSPARC v2.14, and reference-free particle picking was completed using a 491
gaussian blob picker39. Reference-free 2D class averages and ab initio volumes were generated in 492
cryoSPARC, and subsequently 3D-classified to identify classes of S-Fab complexes, that were 493
then homogenously refined. Figures were prepared using UCSF Chimera40. 494
495
.CC-BY-NC-ND 4.0 International licensewas not certified by peer review) is the author/funder. It is made available under aThe copyright holder for this preprint (whichthis version posted May 22, 2020. . https://doi.org/10.1101/2020.05.13.092619doi: bioRxiv preprint
Acknowledgements: We thank all study participants who devoted time to our research; Drs. Barry 496
Coller and Sarah Schlesinger, the Rockefeller University Hospital Clinical Research Support 497
Office and nursing staff. Dr. Joseph L. DeRisi for facilitating interactions with the Chan 498
Zuckerberg BioHub. All members of the M.C.N. laboratory for helpful discussions, Drs. Amelia 499
Escolano, Gaëlle Breton and Bernardo Reis, and Maša Jankovic for laboratory support. This work 500
was supported by NIH grant P01-AI138398-S1 (M.C.N., C.M.R., P.J.B.) and 2U19AI111825 501
(M.C.N. and C.M.R).; the Caltech Merkin Institute for Translational Research and P50 AI150464 502
(P.J.B.), George Mason University Fast Grant and the European ATAC consortium (EC 503
101003650) to D.F.R.; 3 R01-AI091707-10S1 to C.M.R.; R37-AI64003 to P.D.B.; R01AI78788 504
to T.H.; The G. Harold and Leila Y. Mathers Charitable Foundation to C.M.R.. Electron 505
microscopy was performed in the Caltech Beckman Institute Resource Center for Transmission 506
Electron Microscpy (Drs. Songye Chen and Andrey Malyutin, Directors). C.G. was supported by 507
the Robert S. Wennett Post-Doctoral Fellowship, in part by the National Center for Advancing 508
Translational Sciences (National Institutes of Health Clinical and Translational Science Award 509
program, grant UL1 TR001866), and by the Shapiro-Silverberg Fund for the Advancement of 510
Translational Research. P.D.B. and M.C.N. are Howard Hughes Medical Institute Investigators. 511
512
Contributions: D.F.R., P.D.B., P.J.B., T.H., C.M.R. and M.C.N. conceived, designed and 513
analyzed the experiments. D.F.R., M.C. and C.G. designed clinical protocols. F.M., J.C.C.L., 514
Z.W., A.C., M.A., C.O.B., S.F., T.H., C.V., K.G., F.B., S.T.C., P.M., H.H., L.N., F.S., Y.W., H.-515
H.H., E.M., A.W.A., K.E.H.T., N.K. and P.R.H. carried out all experiments. A.G. and M.C. 516
produced antibodies. C.O.B., J.P. and E.W. produced SARS-CoV-2 proteins. A.H., R.K., J.H., 517
K.G.M., C.G. and M.C. recruited participants and executed clinical protocols. R.P., J.D., M.P. and 518
.CC-BY-NC-ND 4.0 International licensewas not certified by peer review) is the author/funder. It is made available under aThe copyright holder for this preprint (whichthis version posted May 22, 2020. . https://doi.org/10.1101/2020.05.13.092619doi: bioRxiv preprint
I.S. processed clinical samples. T.Y.O., A.P.W. and V.R. performed bioinformatic analysis. 519
D.F.R., P.D.B., P.J.B., T.H., C.M.R. and M.C.N. wrote the manuscript with input from all co-520
authors. 521
522
Declaration of conflict: In connection with this work The Rockefeller University has filed a 523
provisional patent application on which D.F.R. and M.C.N. are inventors. 524
.CC-BY-NC-ND 4.0 International licensewas not certified by peer review) is the author/funder. It is made available under aThe copyright holder for this preprint (whichthis version posted May 22, 2020. . https://doi.org/10.1101/2020.05.13.092619doi: bioRxiv preprint
Extended Data Tables 525
526
Extended Data Table 1. Individual participant demographics and clinical characteristics
ID Age Gender Race IgG IgM IgG IgM5 43 M White Non-Hispanic Case 9 41 9 2.52 2.35 5.51 2.43 5.07 40 M White Non-Hispanic Case 11 30 6 2.92 2.54 7.39 2.37 2730.48 37 M White Non-Hispanic Case 3 57 5 2.11 0.81 4.46 0.88 5.09 35 F White Non-Hispanic Case 12 54 5 2.90 1.07 4.44 2.80 5.012 27 F White Non-Hispanic Contact 7 24 3 1.47 1.71 4.31 1.23 5.013 28 M White Non-Hispanic Case 5 25 3 1.97 4.10 3.95 1.38 173.218 55 M White Non-Hispanic Case 16 28 6 2.57 1.75 3.92 1.31 410.320 26 F White Non-Hispanic Case 2 17 5 1.80 2.00 4.49 1.68 5.021 54 M White Hispanic Contact 11 27 7 5.60 2.88 7.60 2.47 5052.724 34 M White Non-Hispanic Case 15 30 4 2.29 1.97 4.36 1.45 280.726 66 M White Non-Hispanic Case 2 35 3 1.67 1.86 4.00 1.58 276.127 28 M White Non-Hispanic Case 9 32 4 1.79 1.64 4.41 1.30 739.328 26 M White Non-Hispanic Case 7 21 4 2.39 2.25 4.93 1.66 888.929 26 F White Non-Hispanic Contact 5 35 4 1.69 1.54 3.93 1.97 5.030 30 M White Non-Hispanic Contact 3 35 4 3.07 2.55 4.86 1.34 5.031 51 M White Non-Hispanic Case 9 33 3 1.29 1.60 4.69 1.20 192.332 46 F White Non-Hispanic Case 8 32 3 1.30 2.18 3.79 0.83 47.437 27 M White Non-Hispanic Case 6 28 6 2.13 1.52 4.11 1.04 286.338 57 F White Non-Hispanic Case 10 38 4 1.87 2.02 4.30 1.12 518.940 44 M White Non-Hispanic Case 7 23 5 1.72 1.50 3.81 1.47 42.141 35 M White Non-Hispanic Contact 10 29 8 2.13 1.67 4.15 0.98 302.542 40 M White Non-Hispanic Contact 20 36 8 2.37 1.50 5.82 1.43 627.145 55 F White Non-Hispanic Case 7 48 6 1.95 0.97 3.53 0.75 5.046 39 M White Non-Hispanic Case 8 30 2 2.68 1.45 4.14 1.29 59.247 43 F White Non-Hispanic Case 11 33 5 3.02 2.30 6.23 2.66 10433.348 37 F White Non-Hispanic Case 7 21 5 1.51 1.85 3.47 1.51 173.450 27 F White Non-Hispanic Contact 7 28 4 1.64 2.32 5.42 1.45 924.751 21 M White Non-Hispanic Contact 8 31 5 1.76 1.69 3.94 1.03 1499.254 40 F White Non-Hispanic Contact 3 24 3 1.80 2.10 4.99 1.42 5.055 36 M White Non-Hispanic Case 3 49 2 1.43 1.23 3.90 2.09 5.056 75 F White Non-Hispanic Case 22 40 3 1.79 1.81 5.89 1.47 1388.457 66 M White Non-Hispanic Case 6 21 5 1.54 2.10 4.33 1.00 2048.958 64 F White Non-Hispanic Contact 1 32 2 1.20 1.71 3.95 1.21 5.064 28 F White Non-Hispanic Contact 11 32 6 2.36 2.06 4.48 1.66 776.767 19 F N/A Hispanic Case 5 29 6 2.56 1.98 5.48 1.32 2052.971 45 F White Non-Hispanic Case 12 48 7 1.55 2.04 3.86 1.53 33.372 42 M White Non-Hispanic Case 16 35 8 4.05 3.58 6.05 2.59 3138.275 46 F White Non-Hispanic Case 10 36 4 1.64 2.37 3.98 1.20 271.576 49 F White Non-Hispanic Case 28 34 4 1.88 1.65 5.17 0.97 219.877 37 M White Non-Hispanic Contact 6 33 4 1.33 1.83 3.56 1.16 5.081 44 F White Non-Hispanic Contact 3 35 2 1.58 1.73 3.82 1.10 5.082 46 M N/A Non-Hispanic Case 0 0 2.19 1.92 5.41 1.81 130.788 41 M White Non-Hispanic Case 7 23 4 1.82 3.32 4.97 1.37 424.795 44 M White Non-Hispanic Case 9 36 6 2.61 1.62 6.03 1.62 961.996 48 F White Non-Hispanic Case 9 30 3 3.93 1.93 6.25 2.26 927.797 39 M White Non-Hispanic Case 9 31 3 1.58 1.61 4.03 2.33 202.798 35 F White Non-Hispanic Case 2 24 4 1.78 1.47 5.38 1.22 249.099 36 F White Non-Hispanic Case 13 29 5 2.50 3.27 4.38 2.49 1127.6
107 53 F White Non-Hispanic Contact 10 29 4 1.74 1.41 4.66 0.90 297.5108 75 M White Non-Hispanic Case 16 41 7 1.37 0.88 3.47 1.36 557.5110 27 M White Non-Hispanic Case 1 25 1 1.30 1.60 4.00 0.93 5.0114 30 F White Non-Hispanic Case 15 36 7 1.65 1.92 3.53 1.55 110.9115 65 F White Non-Hispanic Contact 20 41 6 2.10 3.28 4.32 3.27 1127.7119 56 M White Non-Hispanic Case 13 48 3 1.36 1.26 4.41 1.59 650.3120 56 F White Non-Hispanic Case 26 48 6 0.99 0.97 3.65 1.21 100.6121 19 M White Non-Hispanic Contact 3 42 2 0.85 0.87 3.56 1.26 5.0122 21 F White Non-Hispanic Contact 3 38 1 1.44 0.94 3.39 1.22 5.0123 26 M White Non-Hispanic Contact 12 34 6 0.94 0.95 3.39 1.40 5.0124 63 F Asian Non-Hispanic Contact 4 37 3 1.58 2.06 3.49 1.32 5.0125 51 F White Non-Hispanic Case 10 26 3 1.92 3.49 3.86 1.24 126.5127 24 F White Non-Hispanic Case 10 43 6 1.80 2.50 4.37 2.41 883.5130 39 M White Non-Hispanic Contact 7 28 5 1.24 1.72 3.91 1.34 5.0131 39 M White Non-Hispanic Case 5 25 4 1.46 1.38 4.44 1.03 7.8132 36 M White Non-Hispanic Contact 10 50 6 2.15 1.76 4.84 1.97 5.0134 27 F White Non-Hispanic Contact 16 22 5 2.51 2.18 6.84 1.94 2700.6135 62 F White Non-Hispanic Case 8 31 6 2.20 2.02 3.80 1.13 350.0140 63 F White Non-Hispanic Case 28 47 1 1.05 1.24 3.58 1.28 52.4149 41 M White Non-Hispanic Contact 17 28 6 1.68 2.02 3.67 1.09 494.9150 50 F White Non-Hispanic Contact 12 45 7 1.15 0.43 3.18 1.82 5.0154 68 M Asian Non-Hispanic Case 16 30 9 3.19 2.19 4.85 1.29 928.2157 50 M White Non-Hispanic Case 10 32 8 2.40 2.86 3.90 2.06 741.7166 28 F White Non-Hispanic Case 13 45 2 1.27 0.66 3.45 0.94 5.0167 50 F White Non-Hispanic Contact 11 41 6 1.43 3.71 3.93 8.74 5.0172 38 F White Non-Hispanic Case 8 22 9 1.71 2.58 4.29 1.20 301.1173 47 M White Non-Hispanic Case 5 47 7 2.57 4.14 4.78 4.48 646.9178 26 F White Non-Hispanic Case 6 24 4 1.54 1.59 3.66 1.02 5.0179 39 M White Non-Hispanic Contact 10 37 3 1.89 2.25 3.83 1.73 370.1182 44 F White Non-Hispanic Contact 10 38 6 3.80 1.77 5.36 8.05 1503.7183 43 F White Non-Hispanic Case 13 44 8 1.56 1.02 3.88 1.55 240.1185 54 M White Non-Hispanic Case 11 44 8 3.51 1.39 5.55 2.11 1806.8186 38 F N/A N/A Case 8 26 2 1.73 2.47 4.37 1.23 296.9190 54 F White Non-Hispanic Case 18* 63 9 3.24 1.24 7.38 1.42 598.1195 24 M White Non-Hispanic Case 18 42 5 2.74 2.55 5.01 2.33 1315.1200 60 F White Non-Hispanic Case 17 39 7 2.40 1.00 4.38 1.51 1014.4201 50 M White Non-Hispanic Contact 15 33 6 4.37 2.57 6.15 1.57 3897.4202 57 M White Non-Hispanic Case 21 34 7 2.10 2.08 5.07 1.17 257.9205 64 M White Non-Hispanic Case 7 36 4 4.51 0.70 6.12 1.69 924.4222 28 M Asian Non-Hispanic Case 11 29 7 1.28 0.69 3.94 3.46 5.0229 45 M White Non-Hispanic Case 10 63 4 2.92 1.42 4.90 1.58 1272.9230 50 M White Non-Hispanic Case 18 33 7 3.80 0.47 3.48 0.88 5.0232 38 F White Non-Hispanic Case 13 43 7 1.57 0.70 4.24 5.70 94.3233 55 M White Non-Hispanic Case 20 41 3 2.07 2.11 4.51 1.07 173.2241 36 M White Non-Hispanic Case 12 30 7 2.27 2.66 4.54 1.46 923.1242 59 M White Non-Hispanic Case 10 42 6 4.91 1.94 4.81 2.16 1353.0243 30 F Asian Non-Hispanic Case 6 26 5 2.92 2.57 5.06 1.14 1300.2246 44 F White Non-Hispanic Case 10 38 7 2.05 2.79 6.09 1.32 566.0255 33 M White Non-Hispanic Case 14 44 6 2.14 0.70 4.20 1.24 172.5256 63 F White Non-Hispanic Case 27 42 6 1.72 1.96 4.26 7.79 141.6258 52 M White Non-Hispanic Contact 14 48 6 2.64 1.20 4.52 1.85 4145.9279 41 M White Non-Hispanic Case 7 38 8 1.68 2.13 3.77 1.90 308.9280 59 M White Non-Hispanic Case 6 32 7 2.53 3.07 4.61 1.19 1072.1302 47 F White Non-Hispanic Case 35* 49 7 1.48 0.97 4.06 1.26 5.0310 34 F White Non-Hispanic Case 17 35 5 3.95 1.24 9.44 3.07 485.5314 46 M White Non-Hispanic Case 11 38 7 2.12 0.88 4.56 1.51 667.1315 29 F White Non-Hispanic Case 15 42 8 3.02 0.69 3.98 1.03 376.5319 50 M White Non-Hispanic Case 5 38 6 3.71 2.28 3.79 1.05 5.0323 39 F White Non-Hispanic Case 7 45 7 1.05 1.03 3.53 1.42 5.0325 52 M White Non-Hispanic Case 16 38 8 2.25 1.47 4.83 2.28 1603.3343 21 F White Non-Hispanic Case 16 49 5 1.63 0.94 3.37 1.70 5.0352 44 M White Non-Hispanic Case 16 43 4 3.54 0.92 4.50 1.07 519.2353 60 M White Non-Hispanic Case 14 49 6 5.38 1.12 5.69 1.05 855.5356 22 F White Non-Hispanic Contact 16 38 3 1.37 0.61 2.98 1.09 5.0357 27 F White Non-Hispanic Contact 34 56 5 7.49 1.10 2.77 1.13 5.0364 29 M White Non-Hispanic Contact 14 49 6 0.97 0.58 2.90 0.89 5.0366 41 F White Non-Hispanic Contact 9 34 7 0.98 0.52 3.51 1.19 5.0373 35 F White Non-Hispanic Case 12 51 7 1.69 1.26 5.14 1.69 5.0388 47 F White Non-Hispanic Contact 14 41 9 1.57 1.06 3.61 1.69 5.0393 69 M White Non-Hispanic Case 23* 54 9 1.28 1.74 3.81 2.65 715.4394 48 F Multiple Hispanic Case 7 67 4 2.05 0.87 4.34 2.02 1281.5397 52 M White Non-Hispanic Case 22 45 8 3.32 0.59 5.01 0.87 1516.9403 52 M Asian Non-Hispanic Case 18* 39 10 5.36 1.09 10.01 1.36 3887.8406 65 M White Non-Hispanic Case 20 56 8 4.69 0.90 7.51 1.15 1288.7410 34 M White Non-Hispanic Case 12 46 8 1.06 0.56 3.95 0.76 5.0421 62 F White Non-Hispanic Contact 12 43 9 0.95 1.07 3.34 1.35 5.0426 65 M White Non-Hispanic Case 18 51 6 2.07 0.55 3.95 1.49 804.8437 43 F Asian Non-Hispanic Case 14 34 7 2.54 0.47 4.30 1.44 698.8460 36 M White Non-Hispanic Case 11 39 6 2.94 3.18 5.51 2.80 1906.7461 49 M White Non-Hispanic Case 7 39 5 3.38 0.94 4.67 2.02 1076.6462 28 F White Non-Hispanic Case 16 45 5 1.36 0.38 3.07 1.11 5.0470 28 F White Non-Hispanic Case 17 51 4 1.26 0.86 3.97 1.50 5.0478 31 M White Non-Hispanic Case 16 52 4 1.43 0.93 3.70 1.97 263.2481 28 F Asian Non-Hispanic Case 15 43 8 1.70 0.39 3.46 1.24 5.0486 64 F White Non-Hispanic Case 11 41 10 1.70 1.00 3.68 1.29 5.0500 46 M White Non-Hispanic Case 12 53 5 1.10 0.82 3.49 1.34 5.0501 32 M Asian Non-Hispanic Case 18* 53 10 2.62 0.65 4.51 1.21 718.8502 52 M White Non-Hispanic Case 16* 53 9 5.10 0.61 5.10 1.62 2171.8506 46 M White Non-Hispanic Case 12 59 9 0.84 0.81 3.13 1.21 5.0507 39 M White Non-Hispanic Case 15 60 8 1.92 0.96 4.56 1.52 5.0509 36 M White Non-Hispanic Case 11 50 5 1.99 1.01 3.99 1.45 5.0526 49 M Asian Non-Hispanic Case 11 34 7 3.36 1.45 5.88 1.57 4193.3537 52 M White Non-Hispanic Case 15 45 6 1.47 0.95 3.65 1.58 923.3539 73 F White Non-Hispanic Case 19* 54 10 2.82 0.63 4.46 1.45 487.9547 59 M White Non-Hispanic Case 15* 36 9 2.97 1.53 5.08 2.59 2900.6587 54 M PI N/A Case 17* 51 8 3.22 0.60 4.01 1.49 473.1632 38 M White Non-Hispanic Contact 10 43 6 2.49 0.86 4.50 1.63 572.3633 39 M White Non-Hispanic Contact 8 57 4 1.25 1.04 3.38 1.73 5.0652 76 M White Non-Hispanic Case 18* 56 10 4.75 1.46 8.96 3.80 2324.0664 45 F White Non-Hispanic Case 17* 42 10 1.68 0.43 3.93 1.32 5.0675 47 M White Non-Hispanic Contact 31 47 5 0.79 0.93 2.94 1.38 5.0
*hospitalized, Sx=symptoms
Case/ContactEthnicity
Duration (days) Sx Severity
(0-10)Neutralization
(NT50)Sx
totalSx onset to visit
ELISA binding (AUC)RBD S
.CC-BY-NC-ND 4.0 International licensewas not certified by peer review) is the author/funder. It is made available under aThe copyright holder for this preprint (whichthis version posted May 22, 2020. . https://doi.org/10.1101/2020.05.13.092619doi: bioRxiv preprint
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Extended Data Table 1. Individual participant demographics and clinical characteristics
ID Age Gender Race IgG IgM IgG IgM5 43 M White Non-Hispanic Case 9 41 9 2.52 2.35 5.51 2.43 5.07 40 M White Non-Hispanic Case 11 30 6 2.92 2.54 7.39 2.37 2730.48 37 M White Non-Hispanic Case 3 57 5 2.11 0.81 4.46 0.88 5.09 35 F White Non-Hispanic Case 12 54 5 2.90 1.07 4.44 2.80 5.012 27 F White Non-Hispanic Contact 7 24 3 1.47 1.71 4.31 1.23 5.013 28 M White Non-Hispanic Case 5 25 3 1.97 4.10 3.95 1.38 173.218 55 M White Non-Hispanic Case 16 28 6 2.57 1.75 3.92 1.31 410.320 26 F White Non-Hispanic Case 2 17 5 1.80 2.00 4.49 1.68 5.021 54 M White Hispanic Contact 11 27 7 5.60 2.88 7.60 2.47 5052.724 34 M White Non-Hispanic Case 15 30 4 2.29 1.97 4.36 1.45 280.726 66 M White Non-Hispanic Case 2 35 3 1.67 1.86 4.00 1.58 276.127 28 M White Non-Hispanic Case 9 32 4 1.79 1.64 4.41 1.30 739.328 26 M White Non-Hispanic Case 7 21 4 2.39 2.25 4.93 1.66 888.929 26 F White Non-Hispanic Contact 5 35 4 1.69 1.54 3.93 1.97 5.030 30 M White Non-Hispanic Contact 3 35 4 3.07 2.55 4.86 1.34 5.031 51 M White Non-Hispanic Case 9 33 3 1.29 1.60 4.69 1.20 192.332 46 F White Non-Hispanic Case 8 32 3 1.30 2.18 3.79 0.83 47.437 27 M White Non-Hispanic Case 6 28 6 2.13 1.52 4.11 1.04 286.338 57 F White Non-Hispanic Case 10 38 4 1.87 2.02 4.30 1.12 518.940 44 M White Non-Hispanic Case 7 23 5 1.72 1.50 3.81 1.47 42.141 35 M White Non-Hispanic Contact 10 29 8 2.13 1.67 4.15 0.98 302.542 40 M White Non-Hispanic Contact 20 36 8 2.37 1.50 5.82 1.43 627.145 55 F White Non-Hispanic Case 7 48 6 1.95 0.97 3.53 0.75 5.046 39 M White Non-Hispanic Case 8 30 2 2.68 1.45 4.14 1.29 59.247 43 F White Non-Hispanic Case 11 33 5 3.02 2.30 6.23 2.66 10433.348 37 F White Non-Hispanic Case 7 21 5 1.51 1.85 3.47 1.51 173.450 27 F White Non-Hispanic Contact 7 28 4 1.64 2.32 5.42 1.45 924.751 21 M White Non-Hispanic Contact 8 31 5 1.76 1.69 3.94 1.03 1499.254 40 F White Non-Hispanic Contact 3 24 3 1.80 2.10 4.99 1.42 5.055 36 M White Non-Hispanic Case 3 49 2 1.43 1.23 3.90 2.09 5.056 75 F White Non-Hispanic Case 22 40 3 1.79 1.81 5.89 1.47 1388.457 66 M White Non-Hispanic Case 6 21 5 1.54 2.10 4.33 1.00 2048.958 64 F White Non-Hispanic Contact 1 32 2 1.20 1.71 3.95 1.21 5.064 28 F White Non-Hispanic Contact 11 32 6 2.36 2.06 4.48 1.66 776.767 19 F N/A Hispanic Case 5 29 6 2.56 1.98 5.48 1.32 2052.971 45 F White Non-Hispanic Case 12 48 7 1.55 2.04 3.86 1.53 33.372 42 M White Non-Hispanic Case 16 35 8 4.05 3.58 6.05 2.59 3138.275 46 F White Non-Hispanic Case 10 36 4 1.64 2.37 3.98 1.20 271.576 49 F White Non-Hispanic Case 28 34 4 1.88 1.65 5.17 0.97 219.877 37 M White Non-Hispanic Contact 6 33 4 1.33 1.83 3.56 1.16 5.081 44 F White Non-Hispanic Contact 3 35 2 1.58 1.73 3.82 1.10 5.082 46 M N/A Non-Hispanic Case 0 0 2.19 1.92 5.41 1.81 130.788 41 M White Non-Hispanic Case 7 23 4 1.82 3.32 4.97 1.37 424.795 44 M White Non-Hispanic Case 9 36 6 2.61 1.62 6.03 1.62 961.996 48 F White Non-Hispanic Case 9 30 3 3.93 1.93 6.25 2.26 927.797 39 M White Non-Hispanic Case 9 31 3 1.58 1.61 4.03 2.33 202.798 35 F White Non-Hispanic Case 2 24 4 1.78 1.47 5.38 1.22 249.099 36 F White Non-Hispanic Case 13 29 5 2.50 3.27 4.38 2.49 1127.6
107 53 F White Non-Hispanic Contact 10 29 4 1.74 1.41 4.66 0.90 297.5108 75 M White Non-Hispanic Case 16 41 7 1.37 0.88 3.47 1.36 557.5110 27 M White Non-Hispanic Case 1 25 1 1.30 1.60 4.00 0.93 5.0114 30 F White Non-Hispanic Case 15 36 7 1.65 1.92 3.53 1.55 110.9115 65 F White Non-Hispanic Contact 20 41 6 2.10 3.28 4.32 3.27 1127.7119 56 M White Non-Hispanic Case 13 48 3 1.36 1.26 4.41 1.59 650.3120 56 F White Non-Hispanic Case 26 48 6 0.99 0.97 3.65 1.21 100.6121 19 M White Non-Hispanic Contact 3 42 2 0.85 0.87 3.56 1.26 5.0122 21 F White Non-Hispanic Contact 3 38 1 1.44 0.94 3.39 1.22 5.0123 26 M White Non-Hispanic Contact 12 34 6 0.94 0.95 3.39 1.40 5.0124 63 F Asian Non-Hispanic Contact 4 37 3 1.58 2.06 3.49 1.32 5.0125 51 F White Non-Hispanic Case 10 26 3 1.92 3.49 3.86 1.24 126.5127 24 F White Non-Hispanic Case 10 43 6 1.80 2.50 4.37 2.41 883.5130 39 M White Non-Hispanic Contact 7 28 5 1.24 1.72 3.91 1.34 5.0131 39 M White Non-Hispanic Case 5 25 4 1.46 1.38 4.44 1.03 7.8132 36 M White Non-Hispanic Contact 10 50 6 2.15 1.76 4.84 1.97 5.0134 27 F White Non-Hispanic Contact 16 22 5 2.51 2.18 6.84 1.94 2700.6135 62 F White Non-Hispanic Case 8 31 6 2.20 2.02 3.80 1.13 350.0140 63 F White Non-Hispanic Case 28 47 1 1.05 1.24 3.58 1.28 52.4149 41 M White Non-Hispanic Contact 17 28 6 1.68 2.02 3.67 1.09 494.9150 50 F White Non-Hispanic Contact 12 45 7 1.15 0.43 3.18 1.82 5.0154 68 M Asian Non-Hispanic Case 16 30 9 3.19 2.19 4.85 1.29 928.2157 50 M White Non-Hispanic Case 10 32 8 2.40 2.86 3.90 2.06 741.7166 28 F White Non-Hispanic Case 13 45 2 1.27 0.66 3.45 0.94 5.0167 50 F White Non-Hispanic Contact 11 41 6 1.43 3.71 3.93 8.74 5.0172 38 F White Non-Hispanic Case 8 22 9 1.71 2.58 4.29 1.20 301.1173 47 M White Non-Hispanic Case 5 47 7 2.57 4.14 4.78 4.48 646.9178 26 F White Non-Hispanic Case 6 24 4 1.54 1.59 3.66 1.02 5.0179 39 M White Non-Hispanic Contact 10 37 3 1.89 2.25 3.83 1.73 370.1182 44 F White Non-Hispanic Contact 10 38 6 3.80 1.77 5.36 8.05 1503.7183 43 F White Non-Hispanic Case 13 44 8 1.56 1.02 3.88 1.55 240.1185 54 M White Non-Hispanic Case 11 44 8 3.51 1.39 5.55 2.11 1806.8186 38 F N/A N/A Case 8 26 2 1.73 2.47 4.37 1.23 296.9190 54 F White Non-Hispanic Case 18* 63 9 3.24 1.24 7.38 1.42 598.1195 24 M White Non-Hispanic Case 18 42 5 2.74 2.55 5.01 2.33 1315.1200 60 F White Non-Hispanic Case 17 39 7 2.40 1.00 4.38 1.51 1014.4201 50 M White Non-Hispanic Contact 15 33 6 4.37 2.57 6.15 1.57 3897.4202 57 M White Non-Hispanic Case 21 34 7 2.10 2.08 5.07 1.17 257.9205 64 M White Non-Hispanic Case 7 36 4 4.51 0.70 6.12 1.69 924.4222 28 M Asian Non-Hispanic Case 11 29 7 1.28 0.69 3.94 3.46 5.0229 45 M White Non-Hispanic Case 10 63 4 2.92 1.42 4.90 1.58 1272.9230 50 M White Non-Hispanic Case 18 33 7 3.80 0.47 3.48 0.88 5.0232 38 F White Non-Hispanic Case 13 43 7 1.57 0.70 4.24 5.70 94.3233 55 M White Non-Hispanic Case 20 41 3 2.07 2.11 4.51 1.07 173.2241 36 M White Non-Hispanic Case 12 30 7 2.27 2.66 4.54 1.46 923.1242 59 M White Non-Hispanic Case 10 42 6 4.91 1.94 4.81 2.16 1353.0243 30 F Asian Non-Hispanic Case 6 26 5 2.92 2.57 5.06 1.14 1300.2246 44 F White Non-Hispanic Case 10 38 7 2.05 2.79 6.09 1.32 566.0255 33 M White Non-Hispanic Case 14 44 6 2.14 0.70 4.20 1.24 172.5256 63 F White Non-Hispanic Case 27 42 6 1.72 1.96 4.26 7.79 141.6258 52 M White Non-Hispanic Contact 14 48 6 2.64 1.20 4.52 1.85 4145.9279 41 M White Non-Hispanic Case 7 38 8 1.68 2.13 3.77 1.90 308.9280 59 M White Non-Hispanic Case 6 32 7 2.53 3.07 4.61 1.19 1072.1302 47 F White Non-Hispanic Case 35* 49 7 1.48 0.97 4.06 1.26 5.0310 34 F White Non-Hispanic Case 17 35 5 3.95 1.24 9.44 3.07 485.5314 46 M White Non-Hispanic Case 11 38 7 2.12 0.88 4.56 1.51 667.1315 29 F White Non-Hispanic Case 15 42 8 3.02 0.69 3.98 1.03 376.5319 50 M White Non-Hispanic Case 5 38 6 3.71 2.28 3.79 1.05 5.0323 39 F White Non-Hispanic Case 7 45 7 1.05 1.03 3.53 1.42 5.0325 52 M White Non-Hispanic Case 16 38 8 2.25 1.47 4.83 2.28 1603.3343 21 F White Non-Hispanic Case 16 49 5 1.63 0.94 3.37 1.70 5.0352 44 M White Non-Hispanic Case 16 43 4 3.54 0.92 4.50 1.07 519.2353 60 M White Non-Hispanic Case 14 49 6 5.38 1.12 5.69 1.05 855.5356 22 F White Non-Hispanic Contact 16 38 3 1.37 0.61 2.98 1.09 5.0357 27 F White Non-Hispanic Contact 34 56 5 7.49 1.10 2.77 1.13 5.0364 29 M White Non-Hispanic Contact 14 49 6 0.97 0.58 2.90 0.89 5.0366 41 F White Non-Hispanic Contact 9 34 7 0.98 0.52 3.51 1.19 5.0373 35 F White Non-Hispanic Case 12 51 7 1.69 1.26 5.14 1.69 5.0388 47 F White Non-Hispanic Contact 14 41 9 1.57 1.06 3.61 1.69 5.0393 69 M White Non-Hispanic Case 23* 54 9 1.28 1.74 3.81 2.65 715.4394 48 F Multiple Hispanic Case 7 67 4 2.05 0.87 4.34 2.02 1281.5397 52 M White Non-Hispanic Case 22 45 8 3.32 0.59 5.01 0.87 1516.9403 52 M Asian Non-Hispanic Case 18* 39 10 5.36 1.09 10.01 1.36 3887.8406 65 M White Non-Hispanic Case 20 56 8 4.69 0.90 7.51 1.15 1288.7410 34 M White Non-Hispanic Case 12 46 8 1.06 0.56 3.95 0.76 5.0421 62 F White Non-Hispanic Contact 12 43 9 0.95 1.07 3.34 1.35 5.0426 65 M White Non-Hispanic Case 18 51 6 2.07 0.55 3.95 1.49 804.8437 43 F Asian Non-Hispanic Case 14 34 7 2.54 0.47 4.30 1.44 698.8460 36 M White Non-Hispanic Case 11 39 6 2.94 3.18 5.51 2.80 1906.7461 49 M White Non-Hispanic Case 7 39 5 3.38 0.94 4.67 2.02 1076.6462 28 F White Non-Hispanic Case 16 45 5 1.36 0.38 3.07 1.11 5.0470 28 F White Non-Hispanic Case 17 51 4 1.26 0.86 3.97 1.50 5.0478 31 M White Non-Hispanic Case 16 52 4 1.43 0.93 3.70 1.97 263.2481 28 F Asian Non-Hispanic Case 15 43 8 1.70 0.39 3.46 1.24 5.0486 64 F White Non-Hispanic Case 11 41 10 1.70 1.00 3.68 1.29 5.0500 46 M White Non-Hispanic Case 12 53 5 1.10 0.82 3.49 1.34 5.0501 32 M Asian Non-Hispanic Case 18* 53 10 2.62 0.65 4.51 1.21 718.8502 52 M White Non-Hispanic Case 16* 53 9 5.10 0.61 5.10 1.62 2171.8506 46 M White Non-Hispanic Case 12 59 9 0.84 0.81 3.13 1.21 5.0507 39 M White Non-Hispanic Case 15 60 8 1.92 0.96 4.56 1.52 5.0509 36 M White Non-Hispanic Case 11 50 5 1.99 1.01 3.99 1.45 5.0526 49 M Asian Non-Hispanic Case 11 34 7 3.36 1.45 5.88 1.57 4193.3537 52 M White Non-Hispanic Case 15 45 6 1.47 0.95 3.65 1.58 923.3539 73 F White Non-Hispanic Case 19* 54 10 2.82 0.63 4.46 1.45 487.9547 59 M White Non-Hispanic Case 15* 36 9 2.97 1.53 5.08 2.59 2900.6587 54 M PI N/A Case 17* 51 8 3.22 0.60 4.01 1.49 473.1632 38 M White Non-Hispanic Contact 10 43 6 2.49 0.86 4.50 1.63 572.3633 39 M White Non-Hispanic Contact 8 57 4 1.25 1.04 3.38 1.73 5.0652 76 M White Non-Hispanic Case 18* 56 10 4.75 1.46 8.96 3.80 2324.0664 45 F White Non-Hispanic Case 17* 42 10 1.68 0.43 3.93 1.32 5.0675 47 M White Non-Hispanic Contact 31 47 5 0.79 0.93 2.94 1.38 5.0
*hospitalized, Sx=symptoms
Case/ContactEthnicity
Duration (days) Sx Severity
(0-10)Neutralization
(NT50)Sx
totalSx onset to visit
ELISA binding (AUC)RBD S
.CC-BY-NC-ND 4.0 International licensewas not certified by peer review) is the author/funder. It is made available under aThe copyright holder for this preprint (whichthis version posted May 22, 2020. . https://doi.org/10.1101/2020.05.13.092619doi: bioRxiv preprint
528
Extended Data Table 2. Frequency of symptoms and comorbidities reported by participants
SymptomParticipants
(n=149) %Fever 125 83.9Fatigue 106 71.1Cough 93 62.4Myalgia 92 61.7Shortness of breath 66 44.3Headache 63 42.3Loss of smell/taste 50 33.3Sore throat 38 25.3Diarrhea 32 21.3Presence of comorbidities (HTN, CAD, DM, COPD, asthma, cancer) 16 10.7
HTN (hypertension), CAD (coronary artery disease), DM (diabetes mellitus), COPD (chronic obstructive pulmonary disease)
.CC-BY-NC-ND 4.0 International licensewas not certified by peer review) is the author/funder. It is made available under aThe copyright holder for this preprint (whichthis version posted May 22, 2020. . https://doi.org/10.1101/2020.05.13.092619doi: bioRxiv preprint
Extended Data Tables 3 and 4 are provided as separate Excel files. 529
530
531
Extended data table 5. Sequences of cloned recombinant antibodies
C002 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTATCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATCATATGATGGAAGTAATAAATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAAAGAGGGGAGACCATCTGATATTGTAGTGGTGGTGGCCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLVESGGGVVQPGRSLRLSCAASGFTFSIYGMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKEGRPSDIVVVVAFDYWGQGTLVTVSSGACATCCAGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPRTFGQGTKVEIKC003 GAGGTGCAGCTGGTGGAGTCTGGAGGAGGCTTGATCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGGTTCACCGTCAGTAGCAACTACATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGTTATTTATAGCGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGGGGACACGGCCGTGTATTACTGTGCGAGGGATTACGGTGACTTCTACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLVESGGGLIQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAGDTAVYYCARDYGDFYFDYWGQGTLVTVSSGAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCACCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCACCTAGGACTTTTGGCCAGGGGACCAAGCTGGAGATCAAACEIVLTQSPGTLSLSPGERATLSCRASQSVSSTYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPRTFGQGTKLEIKC004 CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCTGGATACACCTTCACCGGCTACTATATGCACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAACCCTATCAGTGGTGGCACAAACTATGCACAGAAGTTTCAGGGCAGGGTCACCATGACCAGGGACACGTCCATCAGCACAGCCTACATGGAGCTGAGCAGGCTGAGATCTGACGACACGGCCGTGTATTACTGTGCGAGCCCAGCATCACGTGGATATAGTGGCTACGATCATGGGTACTACTACTACATGGACGTCTGGGGCAAAGGGACCACGGTCACCGTCTCCTCAQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPISGGTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCASPASRGYSGYDHGYYYYMDVWGKGTTVTVSSGCCATCCGGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCGAGTCAGGACATTAGCAACTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTACGATGCATCCAATTTGGAAACAGGGGTCCCATCAAGGTTCAGTGGAAGTGGATCTGGGACAGATTTTACTTTCACCATCAGCAGCCTGCAGCCTGAAGATATTGCAACATATTACTGTCAACAGTATGATAATCTCCCTATCACCTTCGGCCAAGGGACACGACTGGAGATTAAACAIRMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPITFGQGTRLEIKC005 CAGGTGCAGCTGGTGCAGTCTGGGCCTGAGGTGAAGAAGCCTGGGACCTCAGTGAAGGTCTCCTGCAAGGCTTCTGGATTCACCTTTACTAGCTCTGCTGTGCAGTGGGTGCGACAGGCTCGTGGACAACGCCTTGAGTGGATAGGATGGATCGTCGTTGGCAGTGGTAACACAAACTACGCACAGAAGTTCCAGGAAAGAGTCACCATTACCAGGGACATGTCCACAAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCCGAGGACACGGCCGTGTATTACTGTGCGGCTCCCCATTGTAGCGGTGGTAGCTGCCTTGATGCTTTTGATATCTGGGGCCAAGGGACAATGGTCACCGTCTCTTCAGQVQLVQSGPEVKKPGTSVKVSCKASGFTFTSSAVQWVRQARGQRLEWIGWIVVGSGNTNYAQKFQERVTITRDMSTSTAYMELSSLRSEDTAVYYCAAPHCSGGSCLDAFDIWGQGTMVTVSSGAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGAAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCACCGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACEIVLTQSPGTLSLSPGERATLSCRASQSVRSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKVEIKC006 CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCAAGCCTGGAGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCATCTTCAGTGACTACTGCATGAGCTGGATCCGCCGGGCTCCAGGGAAGGGGCTGGAATGGCTTTCATATATTAGTAATAGTGGTACCACCAGATACTACGCAGACTCTGTGAAGGGCCGATTCACCATCTCCAGGGACAACGGCAGGAACTCACTGTATCTGCAAATGGACAGCCTGAGCGCCGAAGACACGGCCGTTTATTACTGTGCGAGAAGGGGGGACGGTAGCAGCTCGATCTACTACTACAACTACATGGACGTCTGGGGCAAAGGGACCACGGTCACCGTCTCCTCAQVQLVESGGGLVKPGGSLRLSCAASGFIFSDYCMSWIRRAPGKGLEWLSYISNSGTTRYYADSVKGRFTISRDNGRNSLYLQMDSLSAEDTAVYYCARRGDGSSSIYYYNYMDVWGKGTTVTVSSCAGTCTGTGCTGACTCAGCCACCCTCAGCGTCTGGGACCCCCGGACAGAGGGTCACCGTCTCTTGTTCTGGAAGCAGCTCCAACATCGGAAGCAATACTGTAAACTGGTACCAGCAGCTCCCAGGAACGGCCCCCAAACTCCTCATCTATAGTAATAATCAGCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGGCTGATTATTTCTGTGCAGCATGGGATGACAGCCTGAATGGTCCGGTATTCGGCGGAGGGACCAAGCTGACCGTCCTAGQSVLTQPPSASGTPGQRVTVSCSGSSSNIGSNTVNWYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYFCAAWDDSLNGPVFGGGTKLTVLC008 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGACAGTTATTTCATATGATGGAAGGAATAAATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGAATTCGGTGACCCCGAGTGGTACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVTVISYDGRNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAREFGDPEWYFDYWGQGTLVTVSSGACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCCAATCAGAGTATTAGTAGCTGGTTGGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATAAGGCGTCTAGTTTAGAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAACAGTATAATAGTTATTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACDIQMTQSPSTLSASVGDRVTITCRANQSISSWLAWYQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYWTFGQGTKVEIKC009 CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCATGGCTTCTGGATACACCTTCACCGGCTACTATATGCACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAACCCTAACAGTGGTGGCACAAACTATGCACAGAAGTTTCAGGGCAGGGTCACCATGACCAGGGACACGTCCATCAGCACAGCCTACATGGAGCTGAGCAGGCTGAGATCTGACGACACGGCCGTGTATTACTGTGCGAGAGACTCCCCATTTAGTGCTTTAGGGGCCTCCAATGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGQVQLVQSGAEVKKPGASVKVSCMASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDSPFSALGASNDYWGQGTLVTVSSCAGTCTGCCCTGACTCAGCCTCCCTCCGCGTCCGGGTCTCCTGGACAGTCAGTCACCATCTCCTGCACTGGAACCAGCAGTGACGTTGGTGGTTATAACTATGTCTCCTGGTACCAACAGCACCCAGGCAAAGCCCCCAAACTCATGATTTATGAGGTCAGTAAGCGGCCCTCAGGGGTCCCTGATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCGTCTCTGGGCTCCAGGCTGAGGATGAGGCTGAGTATTACTGCAGCTCAGATGCAGGCAGCAACAATGTGGTATTCGGCGGAGGGACCAAGCTGACCGTCCTAGQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEAEYYCSSDAGSNNVVFGGGTKLTVLC010 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATGCTATGCACTGGGTCCGCCAGGCTCCAGCCAAGGGGCTGGAGTGGGTGGCAGTTATATTATATGATGGAAGCGGTAAATACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGTTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGACGGGATCGTGGATACAGCTCTGGTTACGTGGTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLVESGGGVVQPGRSLRLSCAASGFTFSSYAMHWVRQAPAKGLEWVAVILYDGSGKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGIVDTALVTWFDYWGQGTLVTVSSGACATCCAGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGAGCATTAGCACCTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGTGGACGTTCGGCCAAGGGACCAAGGTGGAGATCAAACDIQLTQSPSSLSASVGDRVTITCRASQSISTYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPWTFGQGTKVEIKC013 CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCTTCTGGAGGCACCTTCAGCAGCTATGCTATCAGCTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAGGGATCATCCCTATCTTTGGTACAGCAAACTACGCACAGAAGTTCCAGGGCAGAGTCACGATTACCGCGGACGAATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCGAGAGGGAATCGACTACTTTATTGTAGTAGTACCAGCTGCTATCTAGATGCGGTTAGGCAGGGGTACTACTACTACTACTACATGGACGTCTGGGGCAAAGGGACCACGGTCACCGTCTCCTCAQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGNRLLYCSSTSCYLDAVRQGYYYYYYMDVWGKGTTVTVSSGAAATTGTGTTGACACAGTCTCCAGCCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCTACTTAGCCTGGTACCAACAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGATGCATCCAACAGGGCCACTGGCATCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGCCTAGAGCCTGAAGATTTTGCAGTTTATTACTGTCAGCAGCGTAGCAACTGGCCCCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPLTFGGGTKVEIKC016 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGATATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATCATATGATGGAAGTAATAAATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAAAGTGACCGCCCCTTATTGTAGTGGTGGTAGCTGCTACGGAGGTAACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLVESGGGVVQPGRSLRLSCAASGFTFSRYGMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKVTAPYCSGGSCYGGNFDYWGQGTLVTVSSGCCATCCGGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCGAGTCAGGACATTAGCAACTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTACGATGCATCCAATTTGGAAACAGGGGTCCCATCAAGGTTCAGCGGAAGTGGATCTGGGACAGATTTTACTTTCACCATCAACAGCCTGCAGCCTGAAGATATTGCAACATATTACTGTCAACAGTATGATAATCTCCCTCCTACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACAIRMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTINSLQPEDIATYYCQQYDNLPPTFGGGTKVEIKC017 GAAGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGCAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTTGATGATTATGCCATGCACTGGGTCCGGCAAGCTCCAGGGAAGGGCCTGGAGTGGGTCTCAGGTATTAGTTGGAATAGTGGTACCATAGGCTATGCGGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAACTCCCTGTATCTGCAAATGAACAGTCTGAGAGCTGAGGACACGGCCTTTTATTACTGTGCAAAAGCGGGCGTAAGGGGTATAGCAGCAGCTGGTCCCGACCTCAACTTCGACCACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGTIGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAFYYCAKAGVRGIAAAGPDLNFDHWGQGTLVTVSSGAAATTGTGTTGACACAGTCTCCAGCCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCTACTTAGCCTGGTACCAACAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGATGCATCCAACAGGGCCACTGGCATCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGCCTAGAGCCTGAAGATTTTGCAGTTTATTACTGTCAGCAGCGTATCACCTTCGGCCAAGGGACACGACTGGAGATTAAACEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRITFGQGTRLEIKC018 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAACTATGCTATACACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATCATATGATGGAAGCAATAAATACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGATTTTGACGATAGTTCGTTCTGGGCGTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLVESGGGVVQPGRSLRLSCAASGFTFSNYAIHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDFDDSSFWAFDYWGQGTLVTVSSGACATCCAGTTGACCCAGTCTCCATCCTCCCTGTCTGCGTCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGAGCATTCGCAGCTATTTAAATTGGTATCAACAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCCCTTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGATGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGGCCACTTTTGGCCAGGGGACCAAGCTGGAGATCAAACDIQLTQSPSSLSASVGDRVTITCRASQSIRSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPDDFATYYCQQSYSTPPATFGQGTKLEIKC019 CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTTTCCTGCAAGGCATCTGGATACACCTTCACCAGTTACTATATGCACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAATAATCAACCCTAGTGGTGGTAGCACAAGCTACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAGGGACACGTCCACGAGCACAGTCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCTAGAGTGCCCCGTGAGGGGACCCCAGGGTTCGACCCCTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGIINPSGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARVPREGTPGFDPWGQGTLVTVSSTCCTATGAGCTGACACAGCCACCCTCAGTGTCAGTGGCCCCAGGAAAGACGGCCAGGATTACCTGTGGGGAAAACAACATTGGAAGTAAAAGTGTGCACTGGTACCAGCAGAAGCCAGGCCAGGCCCCTGTGCTGGTCATCTATTATGATAGCGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCTCCAACTCTGGGAACACGGCCACCCTGACCATCAACAGGGTCGAAGCCGGGGATGAGGCCGACTATTACTGTCAGGTGTGGGATAGTAGTAGTGATCATGTGGTATTCGGCGGAGGGACCAAGCTGACCGTCCTAGSYELTQPPSVSVAPGKTARITCGENNIGSKSVHWYQQKPGQAPVLVIYYDSDRPSGIPERFSGSNSGNTATLTINRVEAGDEADYYCQVWDSSSDHVVFGGGTKLTVLC021 CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCACAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCATCAGCAGTGGTGGTTACTACTGGAGCTGGATCCGCCAGCACCCAGGGAAGGGCCTGGAGTGGATTGGGTACATCTATTACAGTGGGAGCACCTACTACAACCCGTCCCTCAAGAGTCGAGTTACCATATCAGTAGACACGTCTAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACTGCCGCGGACACGGCCGTGTATTACTGTGCGAGAGTTTGGCAATACTATGATAGTAGTGGTTCCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGQVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGYYWSWIRQHPGKGLEWIGYIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARVWQYYDSSGSFDYWGQGTLVTVSSGATATTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTGCAGGTCTAGTCAGAGCCTCCTGCATAGTAATGGATACAACTATTTGGATTGGTACCTGCAGAAGCCAGGGCAGTCTCCACAGCTCCTGATCTATTTGGGTTCTAATCGGGCCTCCGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACACTGAAAATCAGCAGAGTGGAGGCTGAGGATGTTGGGGTTTATTACTGCATGCAAGCTCTACAAACTCCATTCACTTTCGGCCCTGGGACCAAAGTGGATATCAAACDIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPFTFGPGTKVDIKC022 CAGGTGCAGTTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTCCGTCACTTGCACTGTCTCTGGTGGCTCCATCAGCAGTAGTAGGTACTACTGGGGCTGGATCCGCCAGCCCCCAGGGAAGGGGCTGGAGTGGATTGGGAGTATCTATTATAGTGGGAGCACCTACTACAACCCGTCCCTCAAGAGTCGAGTCACCATATCCGTGGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGCCGCAGACACGGCTGTGTATTACTGTGCGAGACATGCGGCAGCATACTATGATAGAAGTGGTTATTATTTCATCGAATACTTCCAGCACTGGGGCCAGGGCACCCTGGTCACCGTCTCCTCAGQVQLQESGPGLVKPSETLSVTCTVSGGSISSSRYYWGWIRQPPGKGLEWIGSIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARHAAAYYDRSGYYFIEYFQHWGQGTLVTVSSGACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGCGTCACCATCACTTGCCGGGCCAGTCAGAGTATTAGTAGCTGGTTGGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATAAGGCGTCTAGTTTAGAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAACAGTATAATAATTACCGGTACACTTTTGGCCAGGGGACCAAGCTGGAGATCAAACDIQMTQSPSTLSASVGDSVTITCRASQSISSWLAWYQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNNYRYTFGQGTKLEIKC027 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATCATATGATGGAAGTAATAAATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAAAGCAAGTGGAATTTATTGTAGTGGTGGAGACTGCTACTCATACTACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKASGIYCSGGDCYSYYFDYWGQGTLVTVSSGACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCCAGTCAGAGTATTAGTAGCTGGTTGGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATAAGGCGTCTAGTTTAGAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAACAGTATAATAGTTATTCGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACDIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYSTFGQGTKVEIKC029 CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCACAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCATCAGCAGTGGTGGTTACTACTGGAGCTGGATCCGCCAGCACCCAGGGAAGGGCCTGGAGTGGATTGGGTACATCTATTACAGTGGGAGCACCTACTACAACCCGTCCCTCAAGAGTCGAGTTACCATATCAGTAGACACGTCTAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACTGCCGCGGACACGGCCGTGTATTACTGTGCGAGAACAATGTATTACTATGATAGTAGTGGTTCCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGQVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGYYWSWIRQHPGKGLEWIGYIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARTMYYYDSSGSFDYWGQGTLVTVSSGATATTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTGCAGGTCTAGTCAGAGCCTCCTGCATAGTAATGGATACAACTATTTGGATTGGTACCTGCAGAAGCCAGGGCAGTCTCCACAGCTCCTGATCTATTTGGGTTCTAATCGGGCCTCCGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACACTGAAAATCAGCAGAGTGGAGGCTGAGGATGTTGGGGTTTATTACTGCATGCAAGCTCTACAAACTCCTCACACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACDIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPHTFGGGTKVEIKC030 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATCATATGATGGAAGTAATAAATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAAAGCAAGTGGAATATATTGTAGTGGTGGTAACTGCTACTCATACTACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKASGIYCSGGNCYSYYFDYWGQGTLVTVSSGACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCCAGTCAGAGTATTAGTAGCTGGTTGGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTCATCTATAAGGCGTCTAGTTTAGAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAACAGTATAATAGTTATTCGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACDIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYSTFGQGTKVEIKC031 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTACGACATGCACTGGGTCCGCCAAGCTACAGGAAAAGGTCTGGAGTGGGTCTCAGCTATTGGTACTGCTGGTGACACATACTATCCAGGCTCCGTGAAGGGCCGATTCACCATCTCCAGAGAAAATGCCAAGAACTCCTTGTATCTTCAAATGAACAGCCTGAGAGCCGGGGACACGGCTGTGTATTACTGTGCAAGAGTAGGGTATGATAGTAGTGGTTATTCGGGCTGGTACTTCGATCTCTGGGGCCGTGGCACCCTGGTCACCGTCTCCTCAGEVQLVESGGGLVQPGGSLRLSCAASGFTFSSYDMHWVRQATGKGLEWVSAIGTAGDTYYPGSVKGRFTISRENAKNSLYLQMNSLRAGDTAVYYCARVGYDSSGYSGWYFDLWGRGTLVTVSSGACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGGTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKVLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPLTFGGGTKVEIKC101 CAGGTGCAGCTGGTGGAGTCTGGAGGAGGCTTGATCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGGTTCATCGTCAGTAGCAACTACATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGTTATTTATAGCGGTGGTAGCACATTCTACACAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACTCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTATTACTGTGTGCGGGACTACGGTGACTTCTACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGQVQLVESGGGLIQPGGSLRLSCAASGFIVSSNYMSWVRQAPGKGLEWVSVIYSGGSTFYTDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCVRDYGDFYFDYWGQGTLVTVSSGAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCGGTGGGTCTGAGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTGTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCACCCCGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACEIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGGGSETDFTLTISRLEPEDCAVYYCQQYGSSPRTFGQGTKVEIKC102 CAGGTGCAGCTGGTGGAGTCTGGAGGAGGCTTGATCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGGTTCATCGTCAGTAGCAACTACATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGTTATTTATAGCGGTGGTAGCACATTCTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTATTACTGTGCGAGGGACTACGGTGACTACTACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGQVQLVESGGGLIQPGGSLRLSCAASGFIVSSNYMSWVRQAPGKGLEWVSVIYSGGSTFYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDYGDYYFDYWGQGTLVTVSSGAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTCTATTACTGTCAGCAGTATGGTAGCTCACCTCGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACEIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPRTFGQGTKVEIKC103 CAGGTGCAGCTACAGCAGTGGGGCGCAGGACTGTTGAAGCCTTCGGAGACCCTGTCCCTCACCTGCGCTGTCTCTGGTGGGTCACTCAGTGGTTTCTACTGGACCTGGATCCGCCAGCCCCCAGGAAAGGGGCTGGAGTGGATTGGGGAAACCAATCATTTTGGAAGCACCGGCTACAAGCCGTCCCTCAAGAGTCGAGTCACCATATCAGTAGACATGTCCAGGAACCAGTTCTCCCTGAAGGTGACCTCTGTGACCGCCGCGGACACGGCTGTGTATTACTGTGCGAGAAAGCCCCTCCTCTACAGTGACTTCTCTCCTGGTGCTTTTGATATCTGGGGCCAAGGGACAATGGTCACCGTCTCTTCAGQVQLQQWGAGLLKPSETLSLTCAVSGGSLSGFYWTWIRQPPGKGLEWIGETNHFGSTGYKPSLKSRVTISVDMSRNQFSLKVTSVTAADTAVYYCARKPLLYSDFSPGAFDIWGQGTMVTVSSGAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGACTGTTACCGCCAACTACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGACTCCTCATCTATGGTGCATCCAAGAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCAGCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATACTACTACACCTCGGACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACEIVLTQSPGTLSLSPGERATLSCRASQTVTANYLAWYQQKPGQAPRLLIYGASKRATGIPDRFSGSGSGTDFTLSISRLEPEDFAVYYCQQYTTTPRTFGGGTKVEIKC104 CAGGTGCAGCTACAGCAGTGGGGCGCAGGACTGTTGAAGCCTTCGGAGACCCTGTCCCTCTCCTGCGCTGTCTATGGTGGGTCCCTCAGTGGTTACTACTGGAGCTGGATCCGCCAGCCCCCAGGGAAGGGGCTGGAGTGGATTGGGGAGATCAATCATTTTGGAAGCACCGGCTACAACCCGTCCCTCAAGAGTCGAGTCACCATCTCCGTGGACACGTCCAAGAGCCAGTTCTCCGTGAAGCTGAGCTCTGTGACCGCCGCGGACACGGCTGTCTATTACTGCGCGAGAAAGCCCCTCCTCTACAGTAACTTATCCCCTGGTGCTTTTGATATCTGGGGCCAAGGGACAATGGTCACCGTCTCTTCAGQVQLQQWGAGLLKPSETLSLSCAVYGGSLSGYYWSWIRQPPGKGLEWIGEINHFGSTGYNPSLKSRVTISVDTSKSQFSVKLSSVTAADTAVYYCARKPLLYSNLSPGAFDIWGQGTMVTVSSGAAATTGTGTTGACGCAGTCTCCAGGCACCGTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCTGGGCCAGTCAGAGTGTTAGCGCCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGTAGACTGGAGCCTGAAGATTTTGCAGTATATTACTGTCAGCAGTACGGTACTACACCTCGGACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACEIVLTQSPGTVSLSPGERATLSCWASQSVSASYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGTTPRTFGGGTKVEIKC105 CAGGTGCAGCTGGTGGAGTCTGGAGGAGGCTTGATCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGGTTCACCGTCAGTAGCAACTACATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGTTATTTATAGCGGTGGTAGTACATACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTATTACTGTGCGAGAGGCGAGGGGTGGGAGCTACCATACGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGQVQLVESGGGLIQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGEGWELPYDYWGQGTLVTVSSCAGTCTGCCCTGACTCAGCCTCCCTCCGCGTCCGGGTCTCCTGGACAGTCAGTCACCATCTCCTGCACTGGAACCAGCAGTGACGTTGGTGGTTATAAGTATGTCTCCTGGTACCAACAGCACCCAGGCAAAGCCCCCAAACTCATGATTTATGAGGTCAGTAAGCGGCCCTCAGGGGTCCCTGATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCGTTTCTGGGCTCCAGGCTGAGGATGAGGCTGATTATTACTGCAGCTCATATGAAGGCAGCAACAATTTTGTGGTATTCGGCGGAGGGACCAAGCTGACCGTCCTAGQSALTQPPSASGSPGQSVTISCTGTSSDVGGYKYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYEGSNNFVVFGGGTKLTVLC106 CAGCTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGCCTCCGTCAGCAGTGGTAGTTACTACTGGAGCTGGATCCGGCAGCCCCCAGGGAAGGGACTGGAATGGATTGGGTATATCTATTACAGTGGGAGCACCAACTACAACCCCTCCCTCAAGAGTCGAGTCACCATATCAGTGGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGCTGCGGACACGGCCGTGTATTACTGTGCGAGAGAGCGGCCCGGTGGAACGTATAGCAACACCTGGTACACCCCAACCGATACCAACTGGTTCGACACCTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGQLQLQESGPGLVKPSETLSLTCTVSGASVSSGSYYWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARERPGGTYSNTWYTPTDTNWFDTWGQGTLVTVSSTCCTATGAGCTGACACAGCCACCCTCAGTGTCAGTGGCCCCAGGAAAGACGGCCAGGATTACCTGTGGGGGAAACAACATTGGAAGTAAAAGTGTGCACTGGTACCAGCAGAAGCCAGGCCAGGCCCCTGTGCTGGTCATCTATTTTGATAGCGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCTCCAACTCTGGGAACACGGCCACCCTGACCATCAGCAGGGTCGAAGCCGGGGATGAGGCCGACTATTACTGTCAGGTGTGGGATAGTAGTCGTGATCATGTGGTATTCGGCGGAGGGACCAAGCTGACCGTCCTAGSYELTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVIYFDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSRDHVVFGGGTKLTVLC107 CAGGTTCAGCTGGTGCAGTCTGGAGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAGGGTCTCCTGCAAGGCTTCTGGTTACACCTTTACCAGCTATGGTTTCAGCTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAGCGCTTACAATGGTAACACAAACTTTGCACAGAAGCTCCAGGGCAGAGTCACCATGACCACAGACACATCCACGAGCACAGCCTACATGGAGCTGAGGAGCCTGAGATCTGACGACACGGCCGTGTATTACTGTGCGAGAGGGGAAGCAGTGGCTGGTACAACCGGTTTTTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGQVQLVQSGAEVKKPGASVRVSCKASGYTFTSYGFSWVRQAPGQGLEWMGWISAYNGNTNFAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARGEAVAGTTGFFDYWGQGTLVTVSSCAGTCTGTGCTGACTCAGCCACCCTCAGCGTCTGGGACCCCCGGGCAGAGGGTCACCATCTCTTGTTCTGGAAGCAGCTCCAACATCGGAAGTAATTATGTATACTGGTACCAGCAGCTCCCAGGAACGGCCCCCAAACTCCTCATCTATAGGAATAATCAGCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCGGTCCGAGGATGAGGCTGATTATTACTGTGCAGCATGGGATGACAGCCTGAGTGGTTTTGTGGTATTCGGCGGAGGGACCAAGCTGACCGTCCTAGQSVLTQPPSASGTPGQRVTISCSGSSSNIGSNYVYWYQQLPGTAPKLLIYRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDSLSGFVVFGGGTKLTVLC108 CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGGGACCCTGTCCCTCACCTGCGCTGTCTCTGGTGGCTCCATCAGCAGTACTAACTGGTGGAGTTGGGTCCGCCAGCCCCCAGGGAAGGGGCTGGAGTGGATTGGGGAAATCTATCATACTGGGAGCACCAACTACAACCCGTCCCTCAAGAGTCGAGTCACCATATCAGTAGACAAGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGCCGCGGACACGGCCGTGTATTACTGTGTGAGAGATGGAGGACGACCCGGGGATGCTTTTGATATCTGGGGCCAAGGGACAATGGTCACCGTCTCTTCAGQVQLQESGPGLVKPSGTLSLTCAVSGGSISSTNWWSWVRQPPGKGLEWIGEIYHTGSTNYNPSLKSRVTISVDKSKNQFSLKLSSVTAADTAVYYCVRDGGRPGDAFDIWGQGTMVTVSSCAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGATCACCATCTCCTGCACTGGAACCAGCAGTGACGTTGGTGGTTATAACTATGTCTCCTGGTACCAACAACACCCAGGCAAAGCCCCCAAACTCATGATTTATGATGTCAGTAATCGGCCCTCAGGGGTTTCTAATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCATCTCTGGGCTCCAGGCTGAGGACGAGGCTGATTATTACTGCAACTCATATACAAGCAGCAGCACTCGAGTCTTCGGAACTGGGACCAAGGTCACCGTCCTAGQSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCNSYTSSSTRVFGTGTKVTVLC109 GAAGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGTAGCTATTGGATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTGGCCAACATAAAGCAAGATGGAAGTGAGAAATACTATGTGGACTCTGTGAAGGGCCGATTCACCATCTCCGGAGACAACGCCAAGAACTCACTGTATCTGCACATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCTATACAGCTATGGTTAAGGGGGGGCTATGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLVESGGGLVQPGGSLRLSCAASGFTFSSYWMSWVRQAPGKGLEWVANIKQDGSEKYYVDSVKGRFTISGDNAKNSLYLHMNSLRAEDTAVYYCAIQLWLRGGYDYWGQGTLVTVSSCAGTCTGCCCTGACTCAGCCTCCCTCCGCGTCCGGGTCTCCTGGACAGTCAGTCACCATCTCCTGCACTGGAACCAGCAGTGACGTTGGTGGTTATAACTATGTCTCCTGGTACCAACAGCACCCAGGCAAAGCCCCCAAACTCATGATTTATGAGGTCACTAAGCGGCCCTCAGGGGTCCCTGATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCGTCTCTGGGCTCCAGGCTGAGGATGAGGCTGATTATTACTGCAGCTCATATGCAGGCAGCAACAATTATGTGGTATTCGGCGGAGGGACCAAGCTGACCGTCCTAGQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVTKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNYVVFGGGTKLTVLC110 CAGGTACAGCTGCAGCAGTCTGGAGCAGAGGTGAAAAAGCCCGGGGAGTCTCTGAAGATCTCCTGTAAGGGTTCTGGATACAGCTTTACCAGCTACTGGATCGGCTGGGTGCGCCAGATGCCCGGGAAAGGCCTGGAGTGGATGGGGATCATCTATCCTGGTGACTCTGATACCAGATACAGCCCGTCCTTCCAAGGCCAGGTCACCATCTCAGCCGACAAGTCCATCAGCACCGCCTACATGCAGTGGAGCAGCCTGAAGGCCTCGGACACCGCCATGTATTACTGTGCGAGATCGTTCCGGGACGACCCCCGTATAGCAGTGGCTGGCCCGGCTGATGCTTTTGATATCTGGGGCCAAGGGACAATGGTCACCGTCTCTTCAGQVQLQQSGAEVKKPGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSISTAYMQWSSLKASDTAMYYCARSFRDDPRIAVAGPADAFDIWGQGTMVTVSSGACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCCAGTCAGAGTATTAGTTACTGGTTGGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATCAGGCGTCTAGTTTAGAAAGTGGGGTCCCGTCAAGGTTCAGCGGCAGTGAGTCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAACAGTATAATAGTTACCCGTACACTTTTGGCCAGGGGACCAAGCTGGAGATCAAACDIQMTQSPSTLSASVGDRVTITCRASQSISYWLAWYQQKPGKAPKLLIYQASSLESGVPSRFSGSESGTEFTLTISSLQPDDFATYYCQQYNSYPYTFGQGTKLEIKC111 CAGCTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCATCAGTAGTTACTACTGGAGCTGGATCCGGCAGCCCCCAGGGAAGGGACTGGAGTGGATTGGGTATATCTATTACAGTGGGAGCACCAACTACAACCCCTCCCTCAAGAGTCGAGTCACCATATCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGCTGCGGACACGGCCGTGTATTACTGTGCGAGAGTAGAAGACTGGGGATATTGTAGTAGTACCAACTGCTATTCTGGTGCTTTTGATATCTGGGGCCAAGGGACAATGGTCACCGTCTCTTCAGQLQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARVEDWGYCSSTNCYSGAFDIWGQGTMVTVSSCAGTCTGTGCTGACGCAGCCACCCTCGGTGTCTGAAGCCCCCAGGCAGAGGGTCACCATCTCCTGTTCTGGAAGCAGCTCCAACATCGGAAATAATGCTGTAAATTGGTACCAGCAGGTCCCAGGAAAGGCTCCCAAACTCCTCATCTATTATGATGATCTGCTGCCCTCAGGGGTCTCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGGCTGATTATTACTGTGCAGCATGGGATGACAGCCTGAATGGCGCTTGGGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTAGQSVLTQPPSVSEAPRQRVTISCSGSSSNIGNNAVNWYQQVPGKAPKLLIYYDDLLPSGVSDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGAWVFGGGTKLTVLC112 CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCCATGCTATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATCATATGATGGAAGCAATAAATACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGAGGATTACTATGATAGTAGTGGTTCTTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGQVQLVESGGGVVQPGRSLRLSCAASGFTFSSHAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAREDYYDSSGSFDYWGQGTLVTVSSCAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGATCACCATCTCCTGCACCGGAACCAGCAGTGACGTTGGTGGTTATAACTATGTCTCCTGGTACCAACAACACCCAGGCAAAGCCCCCAAACTCATGATTTATGATGTCAGTAATCGGCCCTCAGGGGTTTCTAATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCATCTCTGGGCTCCAGGCTGAGGACGAGGCTGATTATTACTGCAGCTCATATACAAGCAGCAGCACTTGGGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTAGQSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTWVFGGGTKLTVLC113 CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTTCAGTAACTTTGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATGGTATGATGGAAGTAATAAATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGGAGTAAACCCCGACGATATTTTGACTGGCGTAGATGCTTTTGATATCTGGGGCCAAGGGACAATGGTCACCGTCTCTTCAGQVQLVESGGGVVQPGRSLRLSCAASGFTFSNFGMHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGVNPDDILTGVDAFDIWGQGTMVTVSSGACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCCAGTCAGAGTATGAGTAGCTGGTTGGCCTGGTATCAGCAGAAACCAGGGAACGCCCCTAAGCTCCTGATCTATAAGGCGTCTAGTTTAGAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAACAGCATAATAGTTCCCCGCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACDIQMTQSPSTLSASVGDRVTITCRASQSMSSWLAWYQQKPGNAPKLLIYKASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQHNSSPLTFGGGTKVEIKC114 CAGGTGCAGCTGGTGGAGTCTGGAGGAGGGTTGATCCAGCCTGGGGGGTCCCTGAAACTCTCCTGTGTAGTCTCTGGGTTCACCGTCAGTAAGAACTACATCAGTTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAATGGGTCTCAGTTATTTTTGCCGGTGGTAGTACATTCTACGCAGACTCCGTTAAGGGCCGATTCGCCATCTCCAGAGACAACTCCAACAACACGCTGTTTCTTCAAATGAACAGCCTGAGAGTCGAGGACACGGCCATTTATTACTGTGCGAGAGGGGACGGGGAGTTATTCTTTGACCAATGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGQVQLVESGGGLIQPGGSLKLSCVVSGFTVSKNYISWVRQAPGKGLEWVSVIFAGGSTFYADSVKGRFAISRDNSNNTLFLQMNSLRVEDTAIYYCARGDGELFFDQWGQGTLVTVSSCAGTCTGTGCTGACTCAGCCGCCCTCAGTGTCTGGGGCCCCAGGGCAGAGGGTCACCATCTCCTGCACTGGGACCAGTTCCAACATCGGGGCAGGTTATGATGTGCACTGGTACCAGCAACTTCCTGGAAGAGCCCCCAAAGTCCTCATCTCTGGAAACAACATTCGGCCCTCAGAGGTCCCTGACCGATTCTCTGGCTCCAGGTCTGGCACCTCAGCCTCCCTGGCCATCACTAGTCTCCAGCCTGAGGATGAGGCTCAATATTACTGTCAGTCTTATGACAGCAGTCTCTATGCGGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTAQSVLTQPPSVSGAPGQRVTISCTGTSSNIGAGYDVHWYQQLPGRAPKVLISGNNIRPSEVPDRFSGSRSGTSASLAITSLQPEDEAQYYCQSYDSSLYAVFGGGTKLTVLC115 CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGATAAAGCCAGGGCGGTCCCTGAGACTCTCTTGTACAGCCTCTGGATTCACCTTTGGTGATTATGCTATGACCTGGTTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTAGGTTTCATTAGAAGTAAAGCTTATGGTGGGACAACAGGATACGCCGCGTCTGTGAAATACAGATTTACCATCTCAAGAGATGATTCCAAAAGCATCGCCTATCTGCAAATGGACAGCCTGAAAACCGAGGACACAGCCGTGTATTACTGTACTAGGTGGGACGGGTGGAGTCAACATGACTATTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGQVQLVESGGGLIKPGRSLRLSCTASGFTFGDYAMTWFRQAPGKGLEWVGFIRSKAYGGTTGYAASVKYRFTISRDDSKSIAYLQMDSLKTEDTAVYYCTRWDGWSQHDYWGQGTLVTVSSGATATTGTGATGACTCAGTCTCCACTCTCCCTGTCCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTGCAGGTCTAGTCAGAGCCTCCTGCATAGTAATGGAAACAACTATTTCGATTGGTACCTGCAGAAGCCAGGGCAGTCTCCACAGCTCCTGATCTATTTGGGTTCTAATCGGGCCTCCGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACACTGAAGATCAGCAGAGTGGAGGCTGAGGATGTTGGGGTTTATTACTGCATGCAAGTTCTACAAATTCCGTACACTTTTGGCCAGGGGACCAAGCTGGAGATCAAACDIVMTQSPLSLSVTPGEPASISCRSSQSLLHSNGNNYFDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQVLQIPYTFGQGTKLEIKC116 CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTACAGTACCTATGCTATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCATTTATATCATATGATGGAAGCAATAAATACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGATTTCTACCATAACTGGTTCGACCCCTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGQVQLVESGGGVVQPGRSLRLSCAASGFTYSTYAMHWVRQAPGKGLEWVAFISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDFYHNWFDPWGQGTLVTVSSAATTTTATGCTGACTCAGCCCCACTCTGTGTCGGAGTCTCCGGGGAAGACGGTAACCATCTCCTGCACCGGCAGCAGTGGCAGCATTGCCAGCAACTATGTGCAGTGGTACCAGCAGCGCCCGGGCAGTGCCCCCACCACTGTGATCTATGAGGATAACCAAAGACCCTCTGGGGTCCCTGATCGGTTCTCTGGCTCCATCGACAGGTCCTCCAACTCTGCCTCCCTCACCATCTCTGGACTGAAGACTGAGGACGAGGCTGACTACTACTGTCAGTCTTATGATAGCGGCAATCATTGGGTGGTATTCGGCGGAGGGACCAGGCTGACCGTCCTAGNFMLTQPHSVSESPGKTVTISCTGSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDRSSNSASLTISGLKTEDEADYYCQSYDSGNHWVVFGGGTRLTVLC117 CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTACCTATGCTATGCACTGGGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGGTGGCAGTTATTTCATATGATGGAAGCAATACATACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAAGACACGGCTGTGTATTACTGTGCGAGAGATCCCATATGGTTCGGGGAGTTATTATCTCCTCCTTTTGTTCACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGQVQLVESGGGVVQPGRSLRLSCAASGFTFSTYAMHWVRQAPGEGLEWVAVISYDGSNTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDPIWFGELLSPPFVHFDYWGQGTLVTVSSCAGTCTGTGCTGACTCAGCCGCCCTCAGTGTCTGCGGCCCCAGGACAGAAGGTCACCATCTCCTGCTCTGGAAGCAGCTCCAACATTGGGAATAATTTGGTATCCTGGTACCAGCAGCTCCCAGGAACAGCCCCCAAACTCCTCATCTATGAAAATAATAAGCGACCCTCAGGGATTCCTGACCGATTCTCTGGCTCCAAGTCTGGCACGTCAGCCACCCTGGGCATCACCGGACTCCAGACTGGGGACGAGGCCGATTATTACTGCGGAGCATGGGATAGCAGCCTGAGTGCTGGCGGGGTTTATGTCTTCGGAACTGGGACCAAGGTCACCGTCCTAGQSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNLVSWYQQLPGTAPKLLIYENNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGAWDSSLSAGGVYVFGTGTKVTVLC118 CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAACTATGCTATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATCATATGATGGAAGCAATAAATACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTATTTATTACTGTGCGAGTGGATATACTGGCTACGATTATTTTGTGCGGGGGGACTACTACGGTCTGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCAQVQLVESGGGVVQPGRSLRLSCAASGFTFSNYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCASGYTGYDYFVRGDYYGLDVWGQGTTVTVSSCAGCCTGTGCTGACTCAATCGCCCTCTGCCTCTGCCTCCCTGGGAGCCTCGGTCAAGCTCACCTGCACTCTGAGCAGTGGGCACAGCAGCTACGCCATCGCATGGCATCAGCAGCAGCCAGAGAAGGGCCCTCGGTACTTGATGAAGCTTAACACTGATGGCAGCCACAGCAAGGGGGACGGGATCCCTGATCGCTTCTCAGGCTCCAGCTCTGGGGCTGAGCGCTACCTCACCATCTCCAGCCTCCAGTCTGAGGATGAGGCTGACTATTACTGTCAGACCTGGGGCACTGGCATTCTCGTATTCGGCGGAGGGACCAAGCTGACCGTCCTAGQPVLTQSPSASASLGASVKLTCTLSSGHSSYAIAWHQQQPEKGPRYLMKLNTDGSHSKGDGIPDRFSGSSSGAERYLTISSLQSEDEADYYCQTWGTGILVFGGGTKLTVLC119 CAGGTCCAGCTGGTACAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTTTCCTGCAAGGCATCTGGATACACCTTCACCAGCTACTATATGCACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAATAATCAACCCTAGTGGTGGTAGCACAAGCTACGCACAGAAGTTACAGGGCAGAGTCACCATGACCAGGGACACGTCCACGAGCACAGTCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCGAGAGCCAATCATGAAACAACTATGGACACTTACTACTACTACTACTACATGGACGTCTGGGGCAAAGGGACCACGGTCACCGTCTCCTCAQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGIINPSGGSTSYAQKLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARANHETTMDTYYYYYYMDVWGKGTTVTVSSCAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGATCACCATCTCCTGCACTGGAACCAGCAGTGACGTTGGTGGTTATAAGTATGTCTCCTGGTACCAACGGCACCCAGGCAAAGCCCCCAAACTCATGATATATGATGTCAGTAATCGGCCCTCAGGGGTTTCTAATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCATCTCTGGGCTCCAGGCTGAGGACGAGGCTGATTATTACTGCAGCTCATACACAAGCAGCAGCACTTCTGTGGTGTTCGGCGGAGGGACCCAGCTGACCGTCCTAGQSALTQPASVSGSPGQSITISCTGTSSDVGGYKYVSWYQRHPGKAPKLMIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTSVVFGGGTQLTVLC120 GAGGTGCAGCTGGTGGAGTCTGGAGGAGGCTTGATCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGGTTCACCGTCAGTAGCAACTACATGACCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCACTTATTTATCCCGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTCTATTACTGTGCGAGAGAGGGTATGGGTATGGCAGCAGCTGGTACGTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLVESGGGLIQPGGSLRLSCAASGFTVSSNYMTWVRQAPGKGLEWVSLIYPGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAREGMGMAAAGTWGQGTLVTVSSGCCATCCGGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACACAGTCACCATCACTTGCCAGGCGAGTCAGGACATTAGCAAGTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTACGATGCATCCAATTTGGAAACAGGGGTCCCATCAAGGTTCAGTGGAAGTGGATCTGGGACAGATTTTACTTTCACCATCAGCAGCCTGCAGCCTGAAGATATTGCAACATATTACTGTCAACAGTATGATAATCTCCCTCAGACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACAIRMTQSPSSLSASVGDTVTITCQASQDISKYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPQTFGGGTKVEIKC121 CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCTGGATACACCTTCACCGGCTACTATATGCACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAGCCCTGTCAGTGGTGGCACAAACTATGCACAGAAGTTTCAGGGCAGGGTCACCATGACCAGGGACACGTCCATCAGCACAGCCTACATGGAGCTGAGCAGGCTGAGATCTGACGACACGGCCGTGTATTACTGTGCGAGAGCCCCACTGTTCCCCACAGGGGTGCTAGCTGGGGACTACTACTACTACGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCAQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWISPVSGGTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARAPLFPTGVLAGDYYYYGMDVWGQGTTVTVSSCAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGATCACCATCTCCTGCACTGGAACCAGCAGTGATGTTGGGAGTTATAACCTTGTCTCCTGGTACCAACAGCACCCAGGCAAAGCCCCCAAACTCATGATTTATGAGGGCAGTAAGCGGCCCTCAGGGGTTTCTAATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACAATCTCTGGACTCCAGGCTGAGGACGAGGCTGATTATTACTGCTGCTCATATGCAGGTAGTAGCACTTTGGTATTCGGCGGAGGGACCAAGCTGACCGTCCTAGQSALTQPASVSGSPGQSITISCTGTSSDVGSYNLVSWYQQHPGKAPKLMIYEGSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCCSYAGSSTLVFGGGTKLTVLC122 GAGGTGCAGCTGGTGGAGTCTGGAGGAGGCTTGATCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGGCTCACCGTCAGTAGCAACTACATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGTTCTTTATAGCGGTGGTAGCTCATTCTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAAGACACGGCCGTGTATTACTGTGCGAGAGAAAGTGGGGATACAACTATGGCCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLVESGGGLIQPGGSLRLSCAASGLTVSSNYMSWVRQAPGKGLEWVSVLYSGGSSFYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARESGDTTMAFDYWGQGTLVTVSSGACATCCAGTTGACCCAGTCTCCATCCTTCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCCAGTCAGGGCATTAGCAGTTATTTAGCCTGGTATCAGCAAAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCACTTTGCAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACAATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTATTACTGTCAACAGCTTAATAGTGACTCGTACACTTTTGGCCAGGGGACCAAGCTGGAGATCAAACDIQLTQSPSFLSASVGDRVTITCRASQGISSYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQQLNSDSYTFGQGTKLEIKC123 GAGGTGCAGCTGGTGGAGTCTGGAGGAGGCTTGATCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGGGTCACCGTCAGTAGGAACTACATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGTTATTTATAGCGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTATTACTGTGCGAGAGATCTATCTGCTGCTTTTGATATCTGGGGCCAAGGGACAATGGTCACCGTCTCTTCAGEVQLVESGGGLIQPGGSLRLSCAASGVTVSRNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSAAFDIWGQGTMVTVSSGACATCCAGTTGACCCAGTCTCCATCCTTCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCCAGTCAGGGCATTAGCAGTTATTTAGCCTGGTATCAGCAAAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCACTTTGCAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACAATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTATTACTGTCAACAGCTTAATAGTTACCCTCCAGCCTTCGGCCAAGGGACACGACTGGAGATTAAACDIQLTQSPSFLSASVGDRVTITCRASQGISSYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQQLNSYPPAFGQGTRLEIKC124 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTGGCTATAGCATGAACTGGGTCCGCCAGGCTCCAGGGAAGGGGCCGGAGTGGGTTTCATACATTAGTAGGAGTAGTAGTACCATATACTACGCAGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAATGCCAAGAACTCACTGTATCTGCAAATGAACAGCCTGAGAGACGAGGACACGGCTGTGTATTACTGTGCGAGAGAAGGGGCTAGAGTGGGAGCTACATATGACACGTACTACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLVESGGGLVQPGGSLRLSCAASGFTFSGYSMNWVRQAPGKGPEWVSYISRSSSTIYYADSVKGRFTISRDNAKNSLYLQMNSLRDEDTAVYYCAREGARVGATYDTYYFDYWGQGTLVTVSSGAAATTGTGTTGACACAGTCTCCAGCCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTTTTAGCAGCTACTTAGCCTGGTACCAACAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGATGCATCCAACAGGGCCACTGGCATCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGCCTAGAGCCTGAAGATTTTGCAGTTTATTACTGTCAGCAGCGTAACAACTGGCCTCCCGAGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACEIVLTQSPATLSLSPGERATLSCRASQSFSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRNNWPPEWTFGQGTKVEIKC125 CAGGTGCAGCTGGTGCAGTCTGGGCCTGAGGTGAAGAAGCCTGGGACCTCAGTGAAGGTCTCCTGCAAGGCTTCTGGATTCACCTTTACTAGCTCTGCTGTGCAGTGGGTGCGACAGGCTCGTGGACAACGCCTTGAGTGGATAGGATGGATCGTCGTTGGCAGTGGTAACACAAACTACGCACAGAAGTTCCAGGAAAGAGTCACCATTACCAGGGACATGTCCACAAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCCGAGGACACGGCCGTGTATTACTGTGCGGCACCTTATTGTAGTGGTGGTAGCTGCTCTGATGCTTTTGATATCTGGGGCCAAGGGACAATGGTCACCGTCTCTTCAGQVQLVQSGPEVKKPGTSVKVSCKASGFTFTSSAVQWVRQARGQRLEWIGWIVVGSGNTNYAQKFQERVTITRDMSTSTAYMELSSLRSEDTAVYYCAAPYCSGGSCSDAFDIWGQGTMVTVSSGAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCACCGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACEIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKVEIKC126 CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTCCCTCTCCTGCGCTGTCTCTGGTGGCTCCATCGGTAGTTACTTCTGGAGCTGGATCCGGCAGCCCCCAGGGAAGGGACTGGAGTGGATTGGATATCTCCATTACAGTGGGAGCACCAACTACAACCCCTCCCTGAAGAGTCGAGTCACCATATCAGTAGACACGTCCAAGAATCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGCTGCGGACACGGCCGTGTATTACTGTGCGAGATTGCAGTGGCTACGCGGAGCTTTTGATATCTGGGGCCAAGGGACAATGGTCACCGTCTCTTCAGQVQLQESGPGLVKPSETLSLSCAVSGGSIGSYFWSWIRQPPGKGLEWIGYLHYSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARLQWLRGAFDIWGQGTMVTVSSAATTTTATGCTGACTCAGCCCCACTCTGTGTCGGAGTCTCCGGGGAAGACGGTAACCATCTCCTGCACCGGCAGCAGTGGCAGCATTGCCAGCAACTATGTGCAGTGGTACCAGCAGCGCCCGGGCAGTGCCCCCACCACTGTGATCAATGAAGATAACCAAAGACCCTCTGGGGTCCCTGATCGGTTCTCTGGCTCCATCGACAGCTCCTCCAACTCTGCCTCCCTCACCATCTCTGGACTGAAGACTGAGGACGAGGCTGACTACTACTGTCAGTCTTATGATAGCAGCAATTTGGTATTCGGCGGAGGGACCAAGCTGACCGTCCTAGNFMLTQPHSVSESPGKTVTISCTGSSGSIASNYVQWYQQRPGSAPTTVINEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSNLVFGGGTKLTVLC127 CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCTGGATACACCTTCACCGGCTACTATATGCACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAACCCTAACAGTGGTGGCACAAACTATGCACAGAAGTTTCAGGGCAGGGTCACCATGACCAGGGACACGTCCATCAGCACAGCCTACATGGAGCTGAGCAGGCTGAGATCTGACGACACGGCCGTGTATTACTGTGCGACGGCGCACCCCCGGAGGATCCAAGGGGTATTTTTTTTGGGGCCGGGCGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCAQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCATAHPRRIQGVFFLGPGVWGQGTTVTVSSCAGTCTGTGCTGACTCAGCCACCCTCAGCGTCTGGGACCCCCGGGCAGAGGGTCACCATCTCTTGTTCTGGAAGCAGCTCCAACATCGGAAGTAATACTGTAAACTGGTACCAGCAGCTCCCAGGAACGGCCCCCAAACTCCTCATCTATAGTAATAATCAGCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGGCTGATTATTACTGTGCAGCATGGGATGACAGCCTGAATGGCGTGGTATTCGGCGGAGGGACCAAGCTGACCGTCCTAGQSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGVVFGGGTKLTVLC128 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCACCTATGCCATGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAACTATTACTGGTAGTGGTCGTGACACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTTTCTGCAACTGAACAGCCTGAGAGCCGAGGACGCGGCCGTGTATTCCTGTGCGAACCACCCTCTGGCATCAGGCGACGACTACTACCACTACTACATGGACGTCTGGGGCAAAGGGACCACGGTCACCGTCTCCTCAEVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMSWVRQAPGKGLEWVSTITGSGRDTYYADSVKGRFTISRDNSKNTLFLQLNSLRAEDAAVYSCANHPLASGDDYYHYYMDVWGKGTTVTVSSGAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAACAGCAGGCAGTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCGTCCAGCAGGGCCACTGGCATCCCAGAGAGGTTCAGTGGCAGTGGATCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGTCTGAAGATTTTGCAGTGTATCACTGTCAGCAATATGGTAGCTCAAGGGCGCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACEIVLTQSPGTLSLSPGERATLSCRASQSVNSRQLAWYQQKPGQAPRLLIYGASSRATGIPERFSGSGSGTDFTLTISRLESEDFAVYHCQQYGSSRALTFGGGTKVEIKC130 CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTTTCCTGCAAGGCATCTGGATACACCTTCACCAACTACTATATGCACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAATAATCAACCCTAGTGGTGGTAGCACAGGCTACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAGGGACACGTCCACGAGCACAGTCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCGAGATCCCGACCGACTCCTGACTGGTACTTCGATCTCTGGGGCCGTGGCACCCTGGTCACCGTCTCCTCAGQVQLVQSGAEVKKPGASVKVSCKASGYTFTNYYMHWVRQAPGQGLEWMGIINPSGGSTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSRPTPDWYFDLWGRGTLVTVSSTCCTATGAGCTGACACAGCCACCCTCAGTGTCAGTGGCCCCAGGAAAGACGGCCAGGATTACCTGTGGGGGAAACAACATTGGAAGTAAAAGTGTGCACTGGTACCAGCAGAAGCCAGGCCAGGCCCCTGTGCTGGTCATCTATTATGATAGCGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCTCCAACTCTGGGAACACGGCCACCCTGACCATCAGCAGGGTCGAAGCCGGGGATGAGGCCGACTATTACTGTCAGGTGTGGGATAGTAGTAGTGATCATCCGGGGGTGGTATTCGGCGGAGGGACCAAGCTGACCGTCCTAGSYELTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVIYYDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHPGVVFGGGTKLTVLC131 CAGGTGCAGCTGGTGCAGTCTGGGTCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCTTCTGGAGGCACCTTCAGCAGCTATGCTTTCAGCTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAAGGATCATCCCTATCCTTGCTTTAGCAAACTACGCACAGAAGTTCCAGGGCAGAGTCACGATTACCGCGGACAAATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCGAGAGTCAATCAAGCAGTAACTACTCCCTTCTCCATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCAQVQLVQSGSEVKKPGSSVKVSCKASGGTFSSYAFSWVRQAPGQGLEWMGRIIPILALANYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCARVNQAVTTPFSMDVWGQGTTVTVSSGAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCTGTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCACCAGGGCCACTGGTATCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGCAGTTTATTACTGTCAGCAGTATAATAACTGGCCGATCACCTTCGGCCAAGGGACACGACTGGAGATTAAACEIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYNNWPITFGQGTRLEIKC132 CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGGGACCCTGTCCCTCACCTGCGCTGTCTCTGGTGGCTCCATCAGCAGTAATAACTGGTGGAGTTGTGTCCGCCAGCCCCCAGGGAAGGGGCTGGAGTGGATTGGGGAAATCTATCATAGTGGGAGCACCAACTACAACCCGTCCCTCAAGAGTCGAGTCACCATATCAGTAGACAAGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGCCGCGGACACGGCCGTGTATTACTGTGCGAGAGGGGGGGATACAGCTATGGGCCCCGAATACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGQVQLQESGPGLVKPSGTLSLTCAVSGGSISSNNWWSCVRQPPGKGLEWIGEIYHSGSTNYNPSLKSRVTISVDKSKNQFSLKLSSVTAADTAVYYCARGGDTAMGPEYFDYWGQGTLVTVSSCAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGATCACCATCTCCTGCACTGGAACCAGCAGTGACGTTGGTGGTTATAACTATGTCTCCTGGTACCAACAACACCCAGGCAAAGCCCCCAAACTCATGATTTATGATGTCAGTAATCGGCCCTCAGGGGTTTCTAATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCATCTCTGGGCTCCAGGCTGAGGACGAGGCTGATTATTACTGCAGCTCATATACAAGCAGCAGCACTCTTTTGTTCGGCGGAGGGACCAAGCTGACCGTCCTAGQSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTLLFGGGTKLTVLC133 CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATGCTATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATTATATGATGGAAGCAATAAATACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGATTCGGACGTAGATACATCTATGGTTACTTGGTTCGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGQVQLVESGGGVVQPGRSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVAVILYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDSDVDTSMVTWFDYWGQGTLVTVSSGACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPWTFGQGTKVEIKC134 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCAACTATGCCATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGGTAGTGATGGTAGCACATACTACGCAGGCTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACACACTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAAAGATCCCCTTATAACTGGACCTACCTATCAATACTTTCACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLLESGGGLVQPGGSLRLSCAASGFTFSNYAMSWVRQAPGKGLEWVSAISGSDGSTYYAGSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDPLITGPTYQYFHYWGQGTLVTVSSTCCTATGAGCTGACACAGCCACCCTCAGTGTCAGTGGCCCCAGGAAAGACGGCCAGGATTACCTGTGGGGGAAACAACATTGGAAGTAAAAGTGTGCACTGGTACCAGCAGAAGCCAGGCCAGGCCCCTGTGCTGGTCATCTATTATGATAGCGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCTCCAACTCTGGGAACACGGCCACCCTGACCATCAGCAGGGTCGAAGCCGGGGATGAGGCCGAATATCACTGTCAGGTGTGGGATAGTAGTAGTGATCGTCCGGGGGTGGTTTTCGGCGGAGGGACCAAGCTGACCGTCCTAGSYELTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVIYYDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEAEYHCQVWDSSSDRPGVVFGGGTKLTVLC135 CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATGCTATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATACCATTTGATGGAAGAAATAAGTACTACGCAGACTCCGTGACGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACACTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGTAGTAGTGGTTATCTTTTCCACTCTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGQVQLVESGGGVVQPGRSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVAVIPFDGRNKYYADSVTGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASSSGYLFHSDYWGQGTLVTVSSGACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCCAGTCAGAGTATTAGTAACTGGTTGGCCTGGTTTCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGAGGCGTCTAGTTTAGAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAACAGTATAATAGTTATCCGTGGACGTTCGGCCAAGGGACCAAGGTGGAGATCAAACDIQMTQSPSTLSASVGDRVTITCRASQSISNWLAWFQQKPGKAPKLLIYEASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYPWTFGQGTKVEIKC138 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGTACCTATTGGATGAGCTGGGTCCGCCAGCCTCCAGGGAAGGGGCTGGAGTGGGTGGCCAACATAAAGCAAGATGGAAGTGAGAAATACTATGTGGATTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAACTCACTGTATCTGCAAATGAACAGCCTGAGAGCCGACGACACGGCCGTGTATTACTGTGCCGGGGGGACATGGCTACGATCCTCTTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLVESGGGLVQPGGSLRLSCAASGFTFSTYWMSWVRQPPGKGLEWVANIKQDGSEKYYVDSVKGRFTISRDNAKNSLYLQMNSLRADDTAVYYCAGGTWLRSSFDYWGQGTLVTVSSAATTTTATGCTGACTCAGCCCCACTCTGTGTCGGAGTCTCCGGGGAAGACGGTAACCATCTCCTGCACCGGCAGCAGTGGCAGCATTGCCAGCAACTATGTGCAGTGGTACCAGCAGCGCCCGGGCAGTGCCCCCACCACTGTGATCTATGAGGATAACCAAAGACCCTCTGGGGTCCCTGATCGGTTCTCTGGCTCCATCGACAGCTCCTCCAACTCTGCCTCCCTCACCATCTCTGGACTGAAGACTGAGGACGAGGCTGACTACTACTGTCAGTCTTATGATAGCAGCAATTGGGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTANFMLTQPHSVSESPGKTVTISCTGSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSNWVFGGGTKLTVLC139 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATGCCATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATCATATGATGGAAGTAATAAATACTCTGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAAAGGGGGGGCCTACAGCTACTACTACTACATGGACGTCTGGGGCAAAGGGACCACGGTCACCGTCTCCTCAEVQLVESGGGVVQPGRSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYSADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKGGAYSYYYYMDVWGKGTTVTVSSGACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCGAGTCAGGACATTAGCAACTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTACGATGCATCCAATTTGGAAACAGGGGTCCCATCAAGGTTCAGTGGAAGTGGATCTGGGACAGATTTTACTTTCACCATCAGCAGCCTGCAGCCTGAAGATATTGCAACATATTACTGTCAACAGTATGATAATCTCCCGCTCACTTTCGGCGGAGGGACCAAGGTGGAAATCAAACDIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGGGTKVEIKC140 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGAGTCACCGTCAGTAGCAACTACATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCACTTATTTATAGCGGTGGTAGCACATTCTACGCAGACTCCGTGAAGGGCAGATTCACCATCTCCAGAGACAATTCCGAGAACACGCTGTATCTTCAAATGAACACCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGATCTGTATTACTACGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCAEVQLVESGGGLVQPGGSLRLSCAASGVTVSSNYMSWVRQAPGKGLEWVSLIYSGGSTFYADSVKGRFTISRDNSENTLYLQMNTLRAEDTAVYYCARDLYYYGMDVWGQGTTVTVSSGACATCCAGTTGACCCAGTCTCCATCCTTCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCCAGTCAGGGCATTAGCAGTTATTTAGCCTGGTATCAGCAAAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCACTTTGCAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACAATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTATTACTGTCAACAGCTTAATAGTTACTCTTACACTTTTGGCCAGGGGACCAAGCTGGAGATCAAACDIQLTQSPSFLSASVGDRVTITCRASQGISSYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQQLNSYSYTFGQGTKLEIKC141 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATGCTATGTTCTGGGTCCGCCAGGCTCCGGGCAAGGGGCTGGAGTGGGTGGCAGTTATATCATATGATGGAAGCAATAAATACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGGGCGGATTTAGGATATTGTACTAATGGTGTATGCTATGTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAEVQLVESGGGVVQPGRSLRLSCAASGFTFSSYAMFWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARADLGYCTNGVCYVDYWGQGTLVTVSSAATTTTATGCTGACTCAGCCCCACTCTGTGTCGGAGTCTCCGGGGAAGACGGTAACCATCTCCTGCACCGGCAGCAGTGGCAGCATTGCCAGCAACTATGTGCAGTGGTACCAGCAGCGCCCGGGCAGTGCCCCCACCACTGTGATCTATGAGGATAACCAAAGACCCTCTGGGGTCCCTGATCGGTTCTCTGGCTCCATCGACAGCTCCTCCAACTCTGCCTCCCTCACCATCTCTGGACTGAAGACTGAGGACGAGGCTGACTACTACTGTCAGTCTTATGATAGCAGCAATTGGGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTAGNFMLTQPHSVSESPGKTVTISCTGSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSNWVFGGGTKLTVLC143 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCGGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCAGTGTCAGCACCAAGTACATGACATGGGTCCGTCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGTTCTTTACAGCGGTGGTAGTGATTACTACGCAGACTCCGTGAAGGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACGCTTTATATCTTCAAATGAACAGCTTGAGAGTCGAGGACACGGGTGTTTATTACTGTGCCAGAGACTCGTCGGAAGTCCGTGACCACCCCGGGCACCCAGGGCGCTCGGTGGGGGCTTTTGATATCTGGGGCCAAGGGACAATGGTCACCGTCTCTTCAGEVQLVESGGGLVQPGGSLRLSCAASGFSVSTKYMTWVRQAPGKGLEWVSVLYSGGSDYYADSVKGRFTISRDNSKNALYLQMNSLRVEDTGVYYCARDSSEVRDHPGHPGRSVGAFDIWGQGTMVTVSSCAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGATCACCATCTCCTGCACTGGAACCAGCAATGATGTTGGGAGTTATACCCTTGTCTCCTGGTACCAACAGTACCCAGGCAAAGCCCCCAAACTCTTAATTTTTGAGGGCACTAAGCGGTCCTCAGGGATTTCTAATCGCTTCTCTGGTTCCAAGTCTGGCAACACGGCCTCCCTGACAATCTCTGGGCTCCAGGGTGAAGACGAGGCTGATTATTATTGCTGCTCATATGCAGGTGCTAGCACTTTCGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTAGQSALTQPASVSGSPGQSITISCTGTSNDVGSYTLVSWYQQYPGKAPKLLIFEGTKRSSGISNRFSGSKSGNTASLTISGLQGEDEADYYCCSYAGASTFVFGGGTKLTVLC144 GAGGTGCAGCTGGTGGAGTCTGGAGGAGGCTTGATCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGGTTCACCGTCAGTAACAACTACATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGTTATTTATAGCGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAAATCCAAGAACACGCTGTATCTTCAAATGAACAGGCTGAGAGCCGAGGACACGGCCGTGTATTATTGTGCGAGAGAAGGGGAGGTAGAAGGGTATAACGATTTTTGGAGTGGTTATTCTAGAGACCGTTACTACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLVESGGGLIQPGGSLRLSCAASGFTVSNNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRDKSKNTLYLQMNRLRAEDTAVYYCAREGEVEGYNDFWSGYSRDRYYFDYWGQGTLVTVSSCAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGATCACCATCTCCTGCACTGGAACCAGCAGTGACGTTGGTGGTTATAACTATGTCTCCTGGTACCAACAACACCCAGGCAAAGCCCCCAAACTCATGATTTATGATGTCAGTAATCGGCCCTCAGGGGTTTCTAATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCATCTCTGGGCTCCAGGCTGAGGACGAGGCTGATTATTACTGCAGCTCATATACAAGCAGCAGCACTCGAGTCTTCGGAACTGGGACCAAGGTCACCGTCCTAGQSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTRVFGTGTKVTVLC145 GAGGTGCAGCTGGTGGAGTCTGGAGGAGGCTTGATCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGGTTCAGCGTCAGTAGCAACTACATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGTTATTTATAGCGGTGGTAGTACATACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTATTACTGTGCGAGAGAAGGGGAGGTAGAAGGGTATTACGATTTTTGGAGTGGTTATTCTAGAGACCGTTACTACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLVESGGGLIQPGGSLRLSCAASGFSVSSNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAREGEVEGYYDFWSGYSRDRYYFDYWGQGTLVTVSSCAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGATCACCATCTCCTGCACTGGAACCAGCAGTGACGTTGGTGGTTATAACTATGTCTCCTGGTACCAACAACACCCAGGCAAAGCCCCCAAACTCATGATTTATGATGTCAGTAATCGGCCCTCAGGGGTTTCTAATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCATCTCTGGGCTCCAGGCTGAGGACGAGGCTGATTATTACTGCAGCTCATATACAAGCAGCACCACTCGAGTCTTCGGAACTGGGACCAGGGTCACCGTCCTAGQSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSTTRVFGTGTRVTVLC146 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCCTGGTCAAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGACTCACCTTCACTGCCTATAGAATGAATTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGCTCTCATCAATTAGTAATACAAATGGCGACATATACTATGCAGACTCAGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAATTCTCTGTATCTGCAAATGAACAGCCTGAGGGCCGACGACACGGCTGTATATTACTGTGCGAGAGATGTTGCATCTAACTACGCTTACTTTGACCTTTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLVESGGGLVKPGGSLRLSCAASGLTFTAYRMNWVRQAPGKGLEWLSSISNTNGDIYYADSVKGRFTISRDNAKNSLYLQMNSLRADDTAVYYCARDVASNYAYFDLWGQGTLVTVSSCAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGATCACCATCTCCTGCACTGGAACCAGCAGTGACATTGGTGTTTATAACTATATCTCCTGGAGCCAACAACACCCAGGCAAAGCCCCCAAAGTCATGATTTATGATGTCACTAATCGGCCCTCAGGGGTTTCTAATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCATCTCTGGGCTCCAGGCTGAGGACGAGGCTGATTATTATTGCAGCTCATATAGAGGCAGCAGCACTCCCTATGTCTTCGGAACTGGGACCAAGGTCACCGTCCTAGQSALTQPASVSGSPGQSITISCTGTSSDIGVYNYISWSQQHPGKAPKVMIYDVTNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYRGSSTPYVFGTGTKVTVLC147 GAGGTGCAGCTGGTGCAGTCTGGAGCAGAGGTGAAAAAGCCCGGGGAGTCTCTGAAGATCTCCTGTAAGGGTTCTGGATACAGATTTACCAACTACTGGATCGGCTGGGTGCGCCAGATGCCCGGGAAAGGCCTGGAGTGGATGGGGATCATCTATCCTGGTGACTCTGATACCAGATACAGCCCGTCCTTCCAAGGCCAGGTCACCATCTCAGCCGACAAGTCCATCACCACCGCCTACCTGCAGTGGAGCAGCCTGAAGGCCTCGGACACCGCCATGTATTACTGTGCGAGACTCAGTGACCGCTGGTACAGTCCGTTCGACCCCTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLVQSGAEVKKPGESLKISCKGSGYRFTNYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSITTAYLQWSSLKASDTAMYYCARLSDRWYSPFDPWGQGTLVTVSSCAGGCTGTGGTGACCCAGGAGCCCTCACTGACTGTGTCCCCAGGAGGGACAGTCACTCTCACCTGTGGCTCCAGCACTGGAGCTGTCACCAGTGGTCATTATCCCTACTGGTTCCAGCAGAAGTCTGGCCAAGCCCCCAGGACACTGATTTATGAAACAAGCATCAAACACTCCTGGACCCCTGCCCGGTTCTCAGGCTCCCTCCTTGGGGGCAAAGCTGCCCTGACCCTTTCGGGTGCGCAGCCTGAGGATGAGGCTGATTATTACTGCTTGCTCTCCTATAGTGGTGCTCGGCCGGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTAGQAVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGHYPYWFQQKSGQAPRTLIYETSIKHSWTPARFSGSLLGGKAALTLSGAQPEDEADYYCLLSYSGARPVFGGGTKLTVLC148 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCAGAGACTCTCCTGTGCAGCCTCTGGATTCACCGTCAGTAGCAATTACATGAGCTGGATCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGTTATTTATAGCGGTGGTAGCGCATACTACGTAGACTCCGTGAAGGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACCCTGTATCTTCAAATGAACAGCCTGAGACCCGAGGACACGGCTGTGTATTACTGTGCGAGAATCGCAAACTACATGGACGTCTGGGGCAAAGGGACCACGGTCACCGTCTCCTCAEVQLVESGGGLVQPGGSQRLSCAASGFTVSSNYMSWIRQAPGKGLEWVSVIYSGGSAYYVDSVKGRFTISRDNSKNTLYLQMNSLRPEDTAVYYCARIANYMDVWGKGTTVTVSSGAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCTGTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCCACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCACCAGGGCCACTGGTATCCCAACCAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGCAGTTTATTACTGCCAGCAGTATAATAACTGGCCTCCGCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACEIVMTQSPATLSVSPGERATLSCRASQSVSSHLAWYQQKPGQAPRLLIYGASTRATGIPTRFSGSGSGTEFTLTISSLQSEDFAVYYCQQYNNWPPLTFGGGTKVEIKC150 GAGGTGCAGCTGGTGGAGTCCGGGGGAGGCTTAGTTCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGTAGCCTCTGGATTCACCTTCAGTAGCTACTGGATGCACTGGGTCCGCCAAGTCCCAGGGAAGGGGCCGGTGTGGGTCTCACATATTAACAGTGAAGGGAGTAGCACAAACTACGCGGACTCCGTGAGGGGCCGATTCACCATCTCCAGAGACAACGCCAAGGACACGCTATATCTTCAAATGAACAATCTGAGAGCCGAGGACACGGCTGTATATTACTGTGCAAGACCGACGGCTGTAGCAGCAGCTGGCAATTACTTCTACTACTACGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCAEVQLVESGGGLVQPGGSLRLSCVASGFTFSSYWMHWVRQVPGKGPVWVSHINSEGSSTNYADSVRGRFTISRDNAKDTLYLQMNNLRAEDTAVYYCARPTAVAAAGNYFYYYGMDVWGQGTTVTVSSCAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGATCACCATCTCCTGCACTGGAACCAGCAGTGACGTTGGTTATTATAACTTTGTCTCCTGGTACCAACAACACCCAGGCAAAGCCCCCAAACTCATGATTTATGAGGTCAGTAATCGGCCCTCTGGGGTTTCTAATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGATCATCTCTGGGCTCCAGGCTGAGGACGAGGCTGATTATTACTGCAGCTCATATAGAAGCAGCAGCACTCTGGTGTTCGGCGGGGGGACCAAGCTGACCGTCCTAGQSALTQPASVSGSPGQSITISCTGTSSDVGYYNFVSWYQQHPGKAPKLMIYEVSNRPSGVSNRFSGSKSGNTASLIISGLQAEDEADYYCSSYRSSSTLVFGGGTKLTVLC151 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCCTGGTCAAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATAACATGAACTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCATGCATTAGTAGTAGTAGTAGTTACATATACTACGCAGACTCAGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAACTCACTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGAGAGGGGGTATGACGGTGGTAAAACCCCCCCATTTCTTGGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLVESGGGLVKPGGSLRLSCAASGFTFSSYNMNWVRQAPGKGLEWVSCISSSSSYIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARERGYDGGKTPPFLGGQGTLVTVSSAATTTTATGCTGACTCAGCCCCACTCTGTGTCGGAGTCTCCGGGGAAGACGGTAACCATCTCCTGCACCGGCAGCAGTGGCAGCATTGCCAGCAACTATGTGCAGTGGTACCAGCAGCGCCCGGGCAGTGCCCCCACCACTGTGATCTATGAGGATAACCAAAGACCCTCTGGGGTCCCTGATCGGTTCTCTGGCTCCATCGACAGCTCCTCCAACTCTGCCTCCCTCACCATCTCTGGACTGAAGACTGAGGACGAGGCTGACTACTACTGTCAGTCTTATGATAGCAGCAATTATTGGGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTAGNFMLTQPHSVSESPGKTVTISCTGSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSNYWVFGGGTKLTVLC153 GAGGTGCAGCTGGTGGAGTCTGGAGGAGGCTTGATCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGGTTCACCGTCAGTAGCAACTACATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGTTATTTATAGCGGTTATAGCACATACTACGTAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTATTACTGTGCGAGAGTGGGGGGAGCACATAGTGGCTACGACGGATCCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLVESGGGLIQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSVIYSGYSTYYVDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVGGAHSGYDGSFDYWGQGTLVTVSSCAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGATCACCATCTCCTGCACTGGAACCAGCAGTGATGTTGGGAGTTATAACCTTGTCTCCTGGTACCAACAGCACCCAGGCAAAGCCCCCAAACTCATGATTTATGAGGGCAGTAAGCGGCCCTCAGGGGTTTCTAATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACAATCTCTGGGCTCCAGGCTGAGGACGAGGCTGATTATTACTGCTGCTCATATGCAGGTAGTAGCACTTGGGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTAGQSALTQPASVSGSPGQSITISCTGTSSDVGSYNLVSWYQQHPGKAPKLMIYEGSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCCSYAGSSTWVFGGGTKLTVLC154 CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTCGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATGTCATATGATGGAAGTAGTAAATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTGTCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAAACAGGCGGGCCCATATTGTAGTGGTGGTAGCTGCTACTCCGCGCCCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGQVQLVESGGGVVQPGRSLRLSCAASGFTFSRYGMHWVRQAPGKGLEWVAVMSYDGSSKYYADSVKGRFTISRDNSKNTLCLQMNSLRAEDTAVYYCAKQAGPYCSGGSCYSAPFDYWGQGTLVTVSSGACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCGAGTCAGGGCATTAGCAACTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTACGATGCATCCAATTTGGAAACAGGGGTCCCATCAAGGTTCAGTGGAAGTGGATCTGGGACAGATTTTACTTTCACCATCAGCAGCCTGCAGCCTGAAGATATTGCAACATATTACTGTCAACAGTATGATAATCTCCCGATCACCTTCGGCCAAGGGACACGACTGGAGATTAAACDIQMTQSPSSLSASVGDRVTITCQASQGISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPITFGQGTRLEIKC155 GAGGTGCAGCTGGTGGAGTCTGGAGGAGGCTTGATCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGGTTCATCGTCAGTAGCAACTACATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGCCTGGAGTGGGTCTCAGTTATTTATAGCGGTGGTAGCACATTCTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTATTACTGTGCGAGAGATTTTGGAGAGTTCTACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLVESGGGLIQPGGSLRLSCAASGFIVSSNYMSWVRQAPGKGLEWVSVIYSGGSTFYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDFGEFYFDYWGQGTLVTVSSGAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCTGTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCACCAGGGCCACTGCTATCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGCAGTTTATTACTGTCAGCAGTATAATAACTGGCCTCGGACGTTCGGCCAAGGGACCAAGGTGGAGATCAAACEIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQKPGQAPRLLIYGASTRATAIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYNNWPRTFGQGTKVEIKC156 CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATCATATGATGGAAATAATAAATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAAAGATCCTTTCCCCTTAGCAGTGGCTGGGACGGGCTACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGQVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAPGKGLEWVAVISYDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDPFPLAVAGTGYFDYWGQGTLVTVSSTCCTATGAGCTGACTCAGCCACCCTCGGTGTCAGTGGCCCCAGGACAGACGGCCAGGATTTCCTGTGGGGGAAACAACATTGGAAGTAAAAATGTGCACTGGTACCAGCAGAAGCCAGGCCAGGCCCCTGTGCTGGTCGTCTATGATGATAGCGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCTCCAACTCTGGGAACACGGCCACCCTGACCATCAGCAGGGTCGAAGCCGGGGATGAGGCCGACTATTACTGTCAGGTGTGGGATAGTAGTAGTGATCCTTGGGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTAGSYELTQPPSVSVAPGQTARISCGGNNIGSKNVHWYQQKPGQAPVLVVYDDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDPWVFGGGTKLTVLC164 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCGGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCAGTGTCAGCACCAAGTACATGACATGGGTCCGTCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGTTCTTTACAGCGGTGGTAGTGATTACTACGCAGACTCCGTGAAGGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACGCTTTATATCTTCAAATGAACAGCTTGAGAGTCGAGGACACGGGTGTTTATTACTGTGCCAGAGACTCGTCGGAAGTCCGTGACCACCCCGGGCACCCAGGGCGCTCGGTGGGGGCTTTTGATATCTGGGGCCAAGGGACAATGGTCACCGTCTCTTCAGEVQLVESGGGLVQPGGSLRLSCAASGFSVSTKYMTWVRQAPGKGLEWVSVLYSGGSDYYADSVKGRFTISRDNSKNALYLQMNSLRVEDTGVYYCARDSSEVRDHPGHPGRSVGAFDIWGQGTMVTVSSCAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGATCACCATCTCCTGCACTGGAACCAGCAATGATGTTGGGAGTTATACCCTTGTCTCCTGGTACCAACAGTACCCAGGCAAAGCCCCCAAGCTCTTAATTTTTGAGGTCACTAAGCGGTCCTCAGGGATTTCTAATCGCTTCTCTGGTTCCAAGTCTGGCAACACGGCCTCCCTGACAATCTCTGGGCTCCAGGGTGAAGACGAGGCTGATTATTATTGCTGCTCATATGCAGGTGCTAGCACTTTCGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTAGQSALTQPASVSGSPGQSITISCTGTSNDVGSYTLVSWYQQYPGKAPKLLIFEVTKRSSGISNRFSGSKSGNTASLTISGLQGEDEADYYCCSYAGASTFVFGGGTKLTVLC165 CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCGTCGGTGAAGGTCTCCTGCAAGGCTTCTGGAGGCACCTTCAGTAGCTATGCTATCAACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAAGGATCATCCCTATCGTTGGTATAGCAAACTACGCACAGAAGTTCCAGGGCAGAGTCACGATTACGGCGGACAAATCCTCGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCGAGAGATCTCCTGGACCCCCAGCTAGATGATGCTTTTGATATCTGGGGCCAAGGGACAATGGTCACCGTCTCTTCAGQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAINWVRQAPGQGLEWMGRIIPIVGIANYAQKFQGRVTITADKSSSTAYMELSSLRSEDTAVYYCARDLLDPQLDDAFDIWGQGTMVTVSSGAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCACCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCACCGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACEIVLTQSPGTLSLSPGERATLSCRASQSVSSTYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKVEIKC201 GAAGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGCAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTTGATGATTATGCCATGCACTGGGTCCGGCAAGCTCCAGGGAAGGGCCTGGAGTGGGTCTCAGGTATTAGTTGGAATAGTGGTAGTATAGGCTATGCGGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAACTCCCTGTATCTGCAAATGAACAGTCTGAGAGCTGAGGAC ACGGCCTTGTATTACTGTGTAAAAGGGGTCGAGTATAGCAGCTCGAGCAACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTALYYCVKGVEYSSSSNFDYWGQGTLVTVSSCATCCGGATGACCCAGTCTCCATCTTCTGTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGTCGGGCGAGTCAGGGTATTAGCAGCTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGTTGAATCCAGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACTATCAGCAGCCTGCAGCCTGAAGATTTTGCAACCTACTATTGTCAACAGGCTAACAGTTTCCCTCTCACTTTCGGCGGAGGGACCAAGGTGGAAATCAAACIRMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLIYVESSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPLTFGGGTKVEIKC202 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTAAGACTCTCCTGTGCAGCCTCTGGATTCACCGTCAGTAGCAACTACATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCACTTATTTATAGCGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGATACCCTTGGTAGGGGGGGCGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSLIYSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDTLGRGGDYWGQGTLVTVSSGACATCCAGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCGAGTCAGGACATTAGCAACTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTACGATGCATCCAATTTGGAAACAGGGGTCCCATCAAGGTTCAGTGGAAGTGGATCTGGGACAGATTTTACTTTCACCATCAGCAGCCTGCAGCCTGAAGATATTGCAACATATTACTGTCAACAGTATGATAATCTCCCTCGGAGTTTTGGCCAGGGGACCAAGCTGGAGATCAAACDIQLTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPRSFGQGTKLEIKC204 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGAACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACTTTTAGCACCTATGCCATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGGTAGTGGTGCTGGCACATTCTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAGAGAGAGCGATTGTGGTAGTACCAGCTGCTATCAAGTCGGGTGGTTCGACCCCTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLLESGGGLEQPGGSLRLSCAASGFTFSTYAMSWVRQAPGKGLEWVSAISGSGAGTFYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARESDCGSTSCYQVGWFDPWGQGTLVTVSSGACATCCAGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGTGGACGTTCGGCCAGGGGACCAAGGTGGAAATCAAACDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPWTFGQGTKVEIKC205 CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTTTCCTGCAAGGCATCTGGACACACCTTCACCAGCTACTATATGCACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAATCATCAACCCTAGTGGTGGTAGCACAAGCTACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAGGGACACGTCCACGAGCACAGTCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCTGTGTATTACTGTGCTAGGGGGCCGGAACGGGGTATAGTGGGAGCTACTGACTACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGQVQLVQSGAEVKKPGASVKVSCKASGHTFTSYYMHWVRQAPGQGLEWMGIINPSGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGPERGIVGATDYFDYWGQGTLVTVSSGAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGTTAGCTCACCGTGGACGTTCGGCCAAGGGACCAAGGTGGAGATCAAACEIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYVSSPWTFGQGTKVEIK C207 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCAGCTATGCCATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGGTAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAAAGAACCCATCGGCCAGCCACTGCTATGGTGGGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKEPIGQPLLWWDYWGQGTLVTVSS GAAATTGTGTTGACACAGTCTCCAGCCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCTACTTAGCCTGGTACCAACAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGATGCATCCAACAGGGCCACTGGCATCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGCCTAGAGCCTGAAGATTTTGCAGTTTATTACTGTCAGCAGCGTAGCAACTGGCCCCGGGGGTTCGGCCAAGGGACCAAGGTGGAGATCAAACEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPRGFGQGTKVEIK C208 GAGGTGCAGCTGGTGCAGTCTGGAGCAGAGGTGAAAAAGCCCGGGGAGTCTCTGAAGATCTCCTGTAAGGGTTCTGGATACAGCTTTACCAGCTACTGGATCGGCTGGGTGCGCCAGATGCCCGGGAAAGGCCTGGAGTGGATGGGGATCATCTATCCTGGTGACTCTGATACCAGATACAGCCCGTCCTTCCAAGGCCAGGTCACCATCTCAGCCGACAAGTCCATCAGCACCGCCTACCTGAAGTGGAGCAGCCTGAAGGCCTCGGACAGCGCCATGTATTACTGTGCGAGGGGGCCCAACCTCCAGAACTGGTTCGACCCCTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLVQSGAEVKKPGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSISTAYLKWSSLKASDSAMYYCARGPNLQNWFDPWGQGTLVTVSS GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCGGCAGCTACTTAGCCTGGTACCAGCAGAGACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCTTCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCGCTCACTTTCGGCGGGGGGACCAAGGTGGAGATCAAACEIVLTQSPGTLSLSPGERATLSCRASQSVSGSYLAWYQQRPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSLTFGGGTKVEIK C209 CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGTCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCTGGATACACCTTCACCAGTTATGATATCAACTGGGTGCGACAGGCCACTGGACAAGGGCTTGAGTGGATGGGATGGATGAACCCTAACAGTGGTAACACAGGCTATGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAGGAACACCTCCATAAGCACAGCCTACATGGANCTGAGCAGCCTGANATCTGANGANACGGCCGTGTATTACTGTGCGANAGGGTTCAGCCTGACTTGGTACTTCGATCTCTGGGGCCGTGGNNCCCTGGTCACCGNCTCCTCAGQVQLVQSGAEVKKSGASVKVSCKASGYTFTSYDINWVRQATGQGLEWMGWMNPNSGNTGYAQKFQGRVTMTRNTSISTAYMXLSSLXSXXTAVYYCAXGFSLTWYFDLWGRGXLVTXSS TCCTATGAGCTGACACAGCCACCCTCGGTGTCAGTGGCCCCAGGAAAGACGGCCAGGATTACCTGTGGGGGAAACAACATTGGAAGCAAAAGTGTGCACTGGTACCAGCAGAAGCCAGGCCATGCCCCTGTACTGGTCGTCTATGATGATAGCGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCTCCAACTCTGGGAACACGGCCACCCTGACCATCAGCAGGGTCGAAGCCGGGGATGAGGCCGACTATTACTGTCAGGTGTGGGATAGTACTGGTGGTCATCCCGATGTGGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTAGSYELTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGHAPVLVVYDDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSTGGHPDVVFGGGTKLTVL C210 GAGGTGCAGCTGGTGGAGTCTGGAGGAGGCTTGATCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGGTTCACCGTCAGTAGCAACTACATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGTTATTTATAGCGGTGGTAGTACATTCTACGCAGACTCCGTGAAGGGCCGATTCACCTTCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTATTACTGTGCGAGAGATTTGATGGCCTACGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCAGEVQLVESGGGLIQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSVIYSGGSTFYADSVKGRFTFSRDNSKNTLYLQMNSLRAEDTAVYYCARDLMAYGMDVWGQGTTVTVSS GACATCCAGTTGACCCAGTCTCCATCCTTCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCCAGTCAGGGCATTAGCAGTTATTTAGCCTGGTATCAGCAAAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCACTTTGCAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACAATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTATTACTGTCAACAGCTTAATAGTTACCCTCAGGGCACTTTCGGCGGAGGGACCAAGGTGGAAATCAAACDIQLTQSPSFLSASVGDRVTITCRASQGISSYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQQLNSYPQGTFGGGTKVEIK C211 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGAATTCACCGTCAGTAGCAACTACATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGTTATTTATAGCGGTGGTAGCACATTCTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGACCTGAGGACACGGCTGTGTATTACTGTGCGAGAGACTACGGTGACTTCTACTTTGACTTCTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLVESGGGLVQPGGSLRLSCAASEFTVSSNYMSWVRQAPGKGLEWVSVIYSGGSTFYADSVKGRFTISRDNSKNTLYLQMNSLRPEDTAVYYCARDYGDFYFDFWGQGTLVTVSS GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCTGTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGGTCCCAGGCTCCTCATCTATGGTGCATCCACCAGGGCCACTGGTATCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGCAGTTTATTACTGTCAGCAGTATAATAACTGGCCCCGGACGTTCGGCCAAGGGACCAAGGTGGAGATCAAACEIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQKPGQGPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYNNWPRTFGQGTKVEIK C212 CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCTGGATACACCGTCACCGGCTATTATATACACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAGCCCTAACAGTGGTGGCACAAACTATGCACAGAAGTTTCAGGGCTGGGTCACCATGACCAGGGACATGTCCATCACCACAGCCTACATGGAGCTGAGTAGACTGAGATCTGACGACACGGCCGTGTATTACTGTGCGAGGGAACGATATTTTGACTTGGGTGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCAGQVQLVQSGAEVKKPGASVKVSCKASGYTVTGYYIHWVRQAPGQGLEWMGWISPNSGGTNYAQKFQGWVTMTRDMSITTAYMELSRLRSDDTAVYYCARERYFDLGGMDVWGQGTTVTVSS CTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGATCACCATCTCCTGCACTGGAACCAGCAGTGATGTTGGGAGTTATAACCTTGTCTCCTGGTACCAACAGCACCCAGGCAAAGCCCCCAAACTCATGATTTATGAGGACAGTAAGCGGCCCTCAGGGGTTTCTAATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACAATCTCTGGGCTCCAGGCTGAGGACGAGGCTGATTATTACTGCTGCTCATATGCAGGTAGTAGCACTCGGCTATTCGGCGGAGGGACCAAGCTGACCGTCCTAGLTQPASVSGSPGQSITISCTGTSSDVGSYNLVSWYQQHPGKAPKLMIYEDSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCCSYAGSSTRLFGGGTKLTVL C214 CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTTCAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGCTATATGGTATGATGGAAGTAATAAACACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGATGTAGGGCGGGTGACGACCTGGTTCGACCCCTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGQVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAAIWYDGSNKHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDVGRVTTWFDPWGQGTLVTVSS GACATCCAGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAACTTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGTGGACGTTCGGCCAAGGGACCAAGGTGGAGATCAAACDIQLTQSPSSLSASVGDRVTITCRASQSISSYLTWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPWTFGQGTKVEIK C215 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCAGCTATGCCATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTACTGATAGTGGTGATGGCACATTCTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTTTATTACTGTGCGTCCGAAGAGGACTACAGTAACTACGTGGGGTGGTTCGACCCCTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGEVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAITDSGDGTFYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASEEDYSNYVGWFDPWGQGTLVTVSS GACATCCAGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTACAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPWTFGQGTKVEIK C216 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTACGACATGCACTGGGTCCGCCAAGCTACAGGAAAAGGTCTGGAGTGGGTCTCAGCTATTGGTACTGCTGGTGACACATACTATCCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGAAAATGCCAAGAACTCCTTGTATCTTCAAATGAACAGCCTGAGAGCCGGGGACACGGCTGTGTATTACTGTGCAAGAGATCGGGGAAGCAGTGGCTGGTACGGCTGGTACTTCGATCTCTGGGGCCGTGGCACCCTGGTCACCGTCTCCTCAGEVQLVESGGGLVQPGGSLRLSCAASGFTFSSYDMHWVRQATGKGLEWVSAIGTAGDTYYPDSVKGRFTISRENAKNSLYLQMNSLRAGDTAVYYCARDRGSSGWYGWYFDLWGRGTLVTVSS GACATCCAGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGTTGCATCCAGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCCCCGATCACCTTCGGCCAAGGGACACGACTGGAGATTAAACDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYVASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK
Antibody ID IGH VDJ (nt) IGH VDJ (aa) IGL VJ (nt) IGL VJ (aa)
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532
Extended Data Table 6. Effective and inhibitory concentrations of the monoclonal antibodies
COV21 C002 8.88 21.95 37.61 3.14 >1000COV21 C003 313.79 992.62 >1000 6.37 >1000COV21 C004 10.67 41.08 91.71 2.39 >1000COV21 C005 60.49 130.65 205.20 4.41 >1000COV21 C006 321.51 >1000 >1000 1.81 >1000COV21 C008 625.46 >1000 >1000 4.63 >1000COV21 C009 4.82 14.54 29.34 1.80 >1000COV21 C010 >1000 >1000 >1000 5.44 >1000COV21 C013 42.48 360.59 >1000 2.59 >1000COV21 C016 >1000 >1000 >1000 7.41 >1000COV21 C017 72.67 256.18 543.87 1.63 >1000COV21 C018 >1000 >1000 >1000 1.53 >1000COV21 C019 >1000 >1000 >1000 11.85 >1000COV21 C021 >1000 >1000 >1000 1.25 >1000COV21 C022 73.57 314.71 736.87 2.40 5.99COV21 C027 >1000 >1000 >1000 2.65 696.05COV21 C029 >1000 >1000 >1000 4.13 >1000COV21 C030 >1000 >1000 >1000 2.89 >1000COV21 C031 >1000 >1000 >1000 22.69 >1000
COV107 C101 8.20 30.15 65.30 1.51 >1000COV107 C102 34.03 84.21 143.23 4.54 >1000COV107 C103 4.38 12.58 23.59 3.77 >1000COV107 C104 23.31 72.12 140.28 8.31 >1000COV107 C105 26.09 72.24 133.70 5.20 >1000COV107 C106 >1000 >1000 >1000 19.03 106.75COV107 C107 >1000 >1000 >1000 11.55 >1000COV107 C108 480.69 >1000 >1000 5.32 >1000COV107 C110 18.44 45.11 77.28 7.29 >1000COV107 C112 111.79 701.99 >1000 3.38 >1000COV107 C113 >1000 >1000 >1000 6.93 >1000COV107 C114 >1000 >1000 >1000 9.51 >1000COV107 C115 198.33 958.18 >1000 3.40 >1000COV107 C116 >1000 >1000 >1000 37.56 >1000COV107 C117 348.00 >1000 >1000 5.38 >1000COV107 C118 103.69 417.76 >1000 3.45 3.817COV107 C119 9.12 39.45 97.78 3.57 >1000COV107 C120 13.26 26.73 40.30 1.41 >1000COV107 C121 6.73 14.31 22.33 2.85 >1000COV107 C122 22.80 57.77 100.12 2.67 >1000COV107 C123 149.22 355.47 595.51 1.92 >1000COV107 C124 341.82 937.26 >1000 2.23 >1000COV107 C125 43.32 92.54 144.26 1.87 >1000COV107 C126 >1000 >1000 >1000 4.78 >1000COV107 C127 68.74 190.96 347.31 2.62 >1000COV072 C128 101.22 263.35 460.73 1.95 >1000COV072 C130 >1000 >1000 >1000 2.05 >1000COV072 C131 30.52 178.90 759.11 1.67 >1000COV072 C132 708.67 >1000 >1000 2.92 >1000COV072 C133 >1000 >1000 >1000 1.98 >1000COV072 C134 >1000 >1000 >1000 1.57 >1000COV072 C135 16.61 32.81 48.90 1.80 >1000COV072 C136 >1000 >1000 >1000 33.61 >1000COV072 C137 >1000 >1000 >1000 25.22 >1000COV072 C138 >1000 >1000 >1000 2.94 >1000COV072 C139 >1000 >1000 >1000 1.89 >1000COV072 C140 23.88 66.24 120.69 2.19 >1000COV072 C141 >1000 >1000 >1000 1.71 >1000COV047 C143 >1000 >1000 >1000 3.66 >1000COV047 C144 6.91 17.28 29.66 3.24 >1000COV047 C145 3.04 14.51 36.79 3.86 >1000COV047 C146 >1000 >1000 >1000 >1000 >1000COV047 C147 >1000 >1000 >1000 >1000 >1000COV047 C148 >1000 >1000 >1000 64.69 >1000COV047 C150 >1000 >1000 >1000 8.11 >1000COV047 C151 31.79 363.97 >1000 4.30 >1000COV047 C153 70.71 490.08 >1000 3.17 >1000COV047 C154 435.50 >1000 >1000 2.92 10.65COV047 C155 11.00 35.75 77.01 3.30 >1000COV047 C156 >1000 >1000 >1000 3.32 >1000COV047 C164 239.15 865.40 >1000 2.06 >1000COV072 C165 40.81 138.66 297.38 4.25 >1000COV96 C201 >1000 >1000 >1000 2.98 >1000COV96 C202 >1000 >1000 >1000 3.40 >1000COV96 C204 >1000 >1000 >1000 3.73 9.41COV96 C205 >1000 >1000 >1000 >1000 >1000COV96 C207 158.52 960.39 >1000 1.87 >1000COV96 C208 >1000 >1000 >1000 >1000 >1000COV96 C209 >1000 >1000 >1000 3.79 >1000COV96 C210 50.73 155.24 298.90 2.83 >1000COV96 C211 12.79 34.87 62.89 2.82 >1000COV96 C212 >1000 >1000 >1000 >1000 >1000COV96 C214 >1000 >1000 >1000 5.75 >1000COV96 C215 >1000 >1000 >1000 5.33 17.944COV96 C216 >1000 >1000 >1000 9.53 >1000
Participant ID Antibody IDSARS-CoV-2 RBD
EC50 ng/mlSARS-CoV RBD
EC50 ng/mlSARS-CoV-2
IC50 ng/mlSARS-CoV-2
IC80 ng/mlSARS-CoV-2
IC90 ng/ml
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Extended Data Figures 533
534
Extended Data Figure 1. Clinical correlates. a, Age distribution (Y axis) for all males and 535
females in the cohort p=0.2074. b, Duration of symptoms in days (Y axis) for all males and females 536
in the cohort p=0.8704. c, Time between symptom onset and plasma collection (Y axis) for all 537
males and females in the cohort p=0.5514. d, Subjective symptom severity on a scale of 0-10 (Y 538
axis) for all males and females in the cohort p=0.1888. e, Age distribution (Y axis) for all cases 539
and contacts in the cohort p=0.0305. f, Duration of symptoms in days (Y axis) for all cases and 540
contacts in the cohort p=0.1241. g, Time between symptom onset and plasma collection in days 541
(Y axis) for all cases and contacts in the cohort p=0.1589. h, Symptom severity (Y axis) for all 542
cases and contacts in the cohort p=0.0550. i, Age distribution (Y axis) for all outpatient and 543
hospitalized participants p=0.0024. j, Duration of symptoms in days (Y axis) for all outpatient and 544
hospitalized participants in the cohort p=<0.0001. k, Time between symptom onset and plasma 545
collection in days (Y axis) for all outpatient and hospitalized participants in the cohort p=0.0001. 546
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l, Symptom severity (Y axis) for all outpatient and hospitalized participants in the cohort 547
p=<0.0001. Horizontal bars indicate median values. Statistical significance was determined using 548
two-tailed Mann-Whitney U test. 549
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550
Extended Data Figure 2. Clinical correlates of plasma antibody titers. a, AUC for IgG anti-551
RBD (Y axis) for all cases and contacts in the cohort p=0.0107. b, AUC for IgM anti-RBD (Y 552
axis) for all cases and contacts in the cohort p=0.5371. c, AUC for IgG anti-S (Y axis) for all cases 553
and contacts in the cohort p=0.0135. d, AUC for IgM anti-S (Y axis) for all cases and contacts in 554
the cohort p=0.7838. e, AUC for IgM anti-RBD (Y axis) for all males and females in the cohort 555
p=0.9597. f, AUC for IgG anti-S (Y axis) for all males and females in the cohort p=0.0275. g, 556
AUC for IgM anti-S (Y axis) for all males and females in the cohort p=0.5363. h, AUC for IgM 557
anti-RBD (Y axis) for all outpatient and hospitalized participants in the cohort p=0.0059. i, AUC 558
for IgG anti-S (Y axis) for all outpatient and hospitalized participants in the cohort p=0.0623. j, 559
AUC for IgM anti-S (Y axis) for all outpatient and hospitalized participants in the cohort p=0.2976. 560
Horizontal bars indicate median values. Statistical significance was determined using two-tailed 561
Mann-Whitney U test. 562
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563
Extended Data Figure 3. Additional clinical correlates of plasma antibody titers. a, Time 564
between symptom onset and plasma collection in days (X axis) plotted against AUC for IgG anti-565
RBD (Y axis) r=-0.0261 p=0.7533. b, Time between symptom onset and plasma collection in days 566
(X axis) plotted against AUC for IgG anti-S (Y axis) r=-0.1495 p=0.0697. c, Time between 567
symptom onset and plasma collection in days (X axis) plotted against AUC for IgM anti-S (Y axis) 568
r=0.1496 p=0.0695. d, Age (X axis) plotted against AUC for IgM anti-RBD (Y axis) r=0.0172 569
p=0.8355. e, Age (X axis) plotted against AUC for IgG anti-S (Y axis) r=0.1523 p=0.0638. f, Age 570
(X axis) plotted against AUC for IgM anti-S (Y axis) r=0.0565 p=0.4934. g, Duration of symptoms 571
in days (X axis) plotted against AUC for IgG anti-RBD (Y axis) r=0.1525, p=0.0633. h, Duration 572
of symptoms in days (X axis) plotted against AUC for IgM anti-RBD (Y axis) r=-0.3187, 573
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p=<0.0001. i, Duration of symptoms in days (X axis) plotted against AUC for IgG anti-S (Y axis) 574
r=0.0329, p=0.6904. j, Duration of symptoms in days (X axis) plotted against AUC for IgM anti-575
S (Y axis) r=0.0824, p=0.3177. k, Severity of symptoms (X axis) plotted against AUC for IgG 576
anti-RBD (Y axis) r=0.2679 p=0.0010. l, Severity of symptoms (X axis) plotted against AUC for 577
IgM anti-RBD (Y axis) r=-0.1943 p=0.0176. m, Severity of symptoms (X axis) plotted against 578
AUC for IgG anti-S (Y axis) r=0.1187 p=0.1492. n, Severity of symptoms (X axis) plotted against 579
AUC for IgM anti-S (Y axis) r=0.1597 p=0.0517. All correlations were analyzed by two-tailed 580
Spearman’s. 581
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582
Extended Data Figure 4. Diagrammatic representation of the SARS-CoV2 pseudovirus 583
luciferase assay. a, Co-transfection of pNL4-3ΔEnv-nanoluc and pSARS-CoV-2 spike vectors 584
into 293T cells leads to production of SARS-CoV-2 Spike-pseudotyped HIV-1 particles (SARS-585
CoV-2 pseudovirus) carrying the Nanoluc gene. b, SARS-CoV-2 pseudovirus is incubated for 1 h 586
at 37°C with plasma or monoclonal antibody dilutions. The virus-antibody mixture is used to infect 587
ACE2-expressing 293T cells, which will express nanoluc Luciferase upon infection. c, Relative 588
luminescence units (RLU) reads from lysates of ACE2-expressing 293T cells infected with 589
increasing amounts of SARS-CoV-2 pseudovirus. 590
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591
Extended Data Figure 5. Clinical correlates of neutralization. a, Anti-RBD IgM AUC (X axis) 592
plotted against NT50 (Y axis) r=0.3119, p=0.0001. b, Anti-S IgM AUC (X axis) plotted against 593
NT50 (Y axis) r=0.3211, p=<0.0001. c, Duration of symptoms in days (X axis) plotted against NT50 594
(Y axis) r=0.1997, p=0.0146. d, Time between symptom onset and plasma collection in days (X 595
axis) plotted against NT50 (Y axis) r=-0.1344, p=0.1033. e, Symptom severity (X axis) plotted 596
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against NT50 (Y axis) r=0.2234, p=0.0062. f, Age (X axis) plotted against NT50 (Y axis) r=0.3005, 597
p=0.0002. All correlations were analyzed by two-tailed Spearman’s. Dotted line (NT50=5) 598
represents lower limit of detection (LLOD) of pseudovirus neutralization assay. Samples with 599
undetectable neutralizing titers were plotted at LLOD. 600
601
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602
Extended Data Figure 6. Flow cytometry. Gating strategy used for cell sorting. Gating was on 603
singlets that were CD20+ and CD3-CD8-CD16-Ova-. Sorted cells were RBD-PE+ and RBD-604
AF647+. 605
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606
Extended Data Figure 7. Frequency distributions of human V genes. The two-tailed t test with 607
unequal variance was used to compare the frequency distributions of human V genes of anti-608
SARS-CoV-2 antibodies from this study to Sequence Read Archive SRP01097034. 609
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610
Extended Data Figure 8. Analysis of antibody somatic hypermutation and CDR3 length. a, 611
For each individual, the number of somatic nucleotide mutations (Y axis) at the IGVH and IGVL 612
are shown on the left panel, and the amino acid length of the CDR3s (Y axis) are shown on the 613
right panel. The horizontal bar indicated the mean. b, same as in a but for all antibodies combined. 614
c, Distribution of the hydrophobicity GRAVY scores at the IGH CDR3 in antibody sequences 615
from this study compared to a public database (see Methods). 616
.CC-BY-NC-ND 4.0 International licensewas not certified by peer review) is the author/funder. It is made available under aThe copyright holder for this preprint (whichthis version posted May 22, 2020. . https://doi.org/10.1101/2020.05.13.092619doi: bioRxiv preprint
617
Extended Data Figure 9. Binding of the monoclonal antibodies to the RBD of SARS-CoV-2 618
and SARS-CoV. a, EC50 values for binding to the RBD of SARS-CoV-2. b and c, Binding curves 619
and EC50 values for binding to the RBD of SARS-CoV. 620
621
.CC-BY-NC-ND 4.0 International licensewas not certified by peer review) is the author/funder. It is made available under aThe copyright holder for this preprint (whichthis version posted May 22, 2020. . https://doi.org/10.1101/2020.05.13.092619doi: bioRxiv preprint
622
Extended Data Figure 10. Biolayer interferometry experiment. showing binding of antibodies 623
C144, C101, C002, C121, C009, C019 (see also main text Fig. 4). Graphs show secondary 624
antibody binding to preformed C121 IgG-RBD complexes. The table displays the shift in 625
nanometers after second antibody (Ab2) binding to the antigen in the presence of the first antibody 626
(Ab1). Values are normalized by the subtraction of the autologous antibody control. 627
628
.CC-BY-NC-ND 4.0 International licensewas not certified by peer review) is the author/funder. It is made available under aThe copyright holder for this preprint (whichthis version posted May 22, 2020. . https://doi.org/10.1101/2020.05.13.092619doi: bioRxiv preprint
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